Fiber reinforced biocomposite medical implants with high mineral content

ABSTRACT

A medical implant comprising a plurality of layers, each layer comprising a polymer and a plurality of uni-directionally aligned continuous reinforcement fibers.

BACKGROUND

Permanent Orthopedic Implant Materials

Medical implants can be manufactured from metals, alloys, ceramics orboth degradable and stable composites. In load-bearing, orthopedicapplications that require high strength, usually stainless steel ortitanium alloys are used. Metal implants have a long history ofsuccessful use in orthopedic surgery but also carry many risks forcomplications. Although these materials are inert, they are also used insituations in which the need for the implant is only temporary, like infracture fixation. In the case of metal rods and plates for fracturefixation, a second surgery for device removal may be recommended aboutone year after confirmation of osseous union. Implant removal causesadditional risk and added morbidity for the patient, occupies theavailability of clinics, and increases the overall procedure costs. Ifthe device is not removed, it may cause remodeling of the bone. Suchremodeling may in turn weaken the bone due to stress shielding orinflammation of the host tissue. The stress shielding can occur due tothe high stiffness (modulus) and strength of the metals compared to thestiffness and strength of the cortical bone, so that the metal stressesthe bone, which can result in periprosthetic fractures or loss of bonestrength.

Examples of load-bearing medical implants that have traditionally beenconstructed of metal alloys include bone plates, rods, screws, tacks,nails, clamps, and pins for the fixation of bone fractures and/orosteotomies to immobilize the bone fragments for healing. Other examplesinclude cervical wedges, lumbar cages and plates and screws forvertebral fusion and other operations in spinal surgery.

Biostable polymers and their composites e.g. based on polymethacrylate(PMMA), ultra high molecular weight polyethylene (UHMWPE),polytetrafluoroethylene (PTFE), polyetheretherketone (PEEK),polysiloxane and acrylic polymers have also been used to manufacturemedical implants. These materials are not biodegradable or bioresorbableand therefore face many of the same limitations as the metals when usedfor medical implant applications, for example they may require a secondsurgery for replacing or removing the implant at some point of thelifetime of the implant. Furthermore, these materials are weaker (lessstrong and stiff) than metal such that they are more susceptible tomechanical failure, particularly after repeated dynamic loading (i.e.through material fatigue or creep).

Existing Degradable Polymer Medical Implants

Resorbable polymers have been used to develop resorbable implants, whichcan also be referred to as absorbable, bioabsorbable, or biodegradableimplants. The advantage of using biocompatible, resorbable polymers isthat the polymers, and thus the implant, resorb in the body and releasenon-toxic degradation products that are metabolized by the metabolicsystem. Polymers, including polylactic and polyglycolic acids andpolydioxanone, are resorbable biocompatible materials that are currentlyused as orthopedic plates, rods, anchors, pins or screws for non-loadbearing medical implant applications, such as craniofacial applications.These medical implant materials offer the advantage of eventualresorption, eliminating the need for later removal, while allowingstress transfer to the remodeling fracture. However, currentbioabsorbable materials and implants do not have mechanical propertiesto match metallic implants. The mechanical strength and modulus(approximately 3-5 GPa) of non-reinforced resorbable polymers, isinsufficient to support fractured cortical bone, which has an elasticmodulus in the range of approximately 15-20 GPa (Snyder S M, et al.measured the bending modulus of human tibial bone to be about 17.5 GPaSnyder S M Schneider E, Journal of Orthopedic Research, Vol. 9, 1991,pp. 422-431). Therefore, the indications of existing medical implantsconstructed from resorbable polymers are limited and their fixationusually requires protection from motion or significant loading. Thesedevices are only a consideration when fixation of low stress areas isneeded (i.e. non-load bearing applications) such as in pediatricpatients or in medial malleolar fractures, syndesmotic fixation,maxillofacial, or osteochondral fractures in adults.

Reinforced Degradable Polymer Materials

Recently, reinforced polymer materials with improved strength andstiffness (modulus) have been introduced. These biodegradable compositescomprise polymers reinforced by fillers, usually in fiber form. Incomposite materials, usually a relatively flexible matrix (i.e. apolymer) is combined with a stiff and strong reinforcement material toenhance the mechanical properties of the composite matrix. For example,biodegradable glass or mineral material can be used to improve thestiffness and strength of a biodegradable polymer matrix. In the priorart, several attempts to produce such a composite were reported wherebioactive glass particles, hydroxyapatite powder, or short glass fiberswere used to enhance the properties of a biodegradable polymer. In mostcases, the strength and stiffness of these composites is lower thancortical bone or becomes lower than cortical bone following rapiddegradation in a physiological environment. Therefore, the majority ofthese composite materials are not appropriate for use in load-bearingmedical implant applications. However, biodegradable composites withstrength and stiffness equivalent to or greater than cortical bone haverecently been reported, for example a biodegradable composite comprisinga biodegradable polymer and 20-70 vol % glass fibers (WO2010128039 A1).Other composite material implants, for example formed of polymerreinforced with fibers, are disclosed in U.S. Pat. Nos. 4,750,905,5,181,930, 5,397,358, 5,009,664, 5,064,439, 4,978,360, 7,419,714, thedisclosures of which are incorporated herein by reference

Degradation Mechanism of Reinforced Degradable Polymer Materials

When biodegradable composites are used for load-bearing medical implantapplications, such as to fixate bone fractures, the mechanicalproperties of the medical implant must be retained for an extendedperiod. Degradation of the composite will result in premature loss ofimplant strength or stiffness and can lead to implant function failure,such as insufficient fixation of bone segments resulting in improperbone healing.

Biodegradable composites will begin to hydrolytically degrade once theycome into contact with body fluid. This degradation can be a result ofdegradation of the biodegradable polymer, reinforcing filler, or both.Such degradation in an aqueous environment, such as the physiologicalenvironment, can particularly result in a sharp drop-off of mechanicalstrength and stiffness in certain reinforced polymer materials that arereinforced by inorganic compounds. Where the absorbable polymer matrixis organic material, and the fillers are inorganic compounds, theadhesion between the absorbable polymer matrix and the filler may bereduced by degradation of either the polymer or filler in the aqueousenvironment and become rapidly reduced such that the initial mechanicalproperties of the reinforced polymer drop-off rapidly and become lessthan desirable for adequate load-bearing performance. Aside from thedegradation of the polymer and filler separately, poor polymer toreinforcement interface interaction and adhesion can result in earlyfailure at the interface in a aqueous environment, thereby resulting insharp mechanical property drop off as the reinforcement detaches fromthe polymer and the reinforcing effect of the filler is lost.

Törmälä et al. (WO 2006/114483) described a composite materialcontaining two reinforcing fibers, one polymeric and one ceramic, in apolymer matrix and reported good initial mechanical results (bendingstrength of 420+/−39 MPa and bending modulus of 21.5 GPa) equivalent tothe properties of cortical bone. However, the prior art teaches thatbioabsorbable composites reinforced with absorbable glass fibers, have ahigh initial bending modulus but that they rapidly lose their strengthand modulus in vitro.

While improved interfacial bonding (such as covalent bonding) betweenthe polymer and reinforcement can significantly prolong reinforcedbioabsorbable polymer mechanical property retention in an aqueousenvironment (WO2010128039 A1), continued hydrolysis of the polymer,reinforcement, or interface between the two will result in loss ofmechanical properties over time. Since osseous union may take severalmonths or longer, even the prolonged mechanical property degradationprofile in covalently bonded reinforced bioabsorbable polymers may beinsufficient for optimal function of medical implants used forload-bearing orthopedic applications.

An example of strength loss in a reinforced degradable polymer implantis described with regard to self-reinforced poly-L-lactic acid (Majola Aet al., Journal of Materials Science Materials in Medicine, Vol. 3,1992, pp. 43-47). There, the strength and strength retention ofself-reinforced poly-L-lactic acid (SR-PLLA) composite rods wereevaluated after intramedullary and subcutaneous implantation in rabbits.The initial bending strength of the SR-PLLA rods was 250-271 MPa. Afterintramedullary and subcutaneous implantation of 12 weeks the bendingstrength of the SR-PLLA implants was 100 MPa.

Co- and terpolyesters of PLA, PGA and PCL are of interest in thetailoring of the optimal polymer for resorbable composite material formedical devices. The choice of monomer ratio and molecular weightsignificantly affects the strength elasticity, modulus, thermalproperties, degradation rate and melt viscosity of resorbable compositematerials and all of these polymers are known to be degradable inaqueous conditions, both in vitro and in vivo. Two stages have beenidentified in the degradation process: First, degradation proceeds byrandom hydrolytic chain scission of the ester linkages which decreasesthe molecular weight of the polymers. In the second stage measurableweight loss in addition to chain scission is observed. The mechanicalproperties are mainly lost or at least a remarkable drop will be seen inthem at the point where weight loss starts. Degradation rate of thesepolymers is different depending on the polymer structure: crystallinity,molecular weight, glass transition temperature, block length,racemization and chain architecture. (Middleton J C, Tipton A J,Biomaterials 21, 2000, 2335-2346)

The Unsolved Problem of Mineral Content in Orthopedic Implants

As previously described, attempts have been made to produce orthopedicfixation implants from bioabsorbable polymers such as poly lactic acid(PLA). However, these implants derived their mechanical propertiessolely from the PLA acidic polymer chains. Thus, their strength waslimited (a fraction of the strength and modulus of bone) and the acidicburst degradation process of these bioabsorbable polymer implantsresulted in problematic local tissue response (cysts, abcesses, etc).The bone attachment to these implants was poor.

Manufacturers have responded to the inflammatory local tissue responseand poor bone attachment of bioabsorbable fixation devices by mixingvarious mineral compositions into the bioabsorbable polymercompositions. For mineral compositions, companies have used minerals ormineral compositions with osteoconductive properties. Some useTricalcium phosphate, some use hydroxyapatite, some use calcium sulfate,some use mixtures of these. These mixed composition implants are called“biocomposite” implants and incorporate 25-35% mineral and the mineralpowder is evenly distributed into the polymer composition.

Unfortunately, the mineral additive in these biocomposite implantsreduces the mechanical properties of the implants since the mechanicalstrength of these implants derives from the bioabsorbable polymer andthere is less polymer in the implant once the mineral composition hasbeen added. Thus, biocomposite implants tend to be more brittle thanequivalent implants comprised entirely of bioabsorbable polymers. Higheramounts of mineral than the existing 25-35% cannot be used since theimplant will be lacking in mechanical properties.

On the other hand, without the mineral composition, the long termimplantation results of existing biocomposite implants are problematic.These implants still suffer from the inflammatory tissue response thathas plagued bioabsorbable polymer implants. For example, in ACLinterference screws comprised of biocomposite compositions, it has beendemonstrated (Cox C L et al. J Bone Joint Surg Am. 2014; 96:244-50) thatbiocomposite screws result in a very high percentage of inflammatoryreactions (cysts, edema). Furthermore, they don't really encouragebiointegration. As the article concludes “Even though thesenewer-generation bioabsorbable screws were designed to promote osseousintegration, no tunnel narrowing was noted”.

Besides for these inflammatory problems, the current biocomposite screwsalso are lacking in sufficient mechanical properties (Mascarenhas et al.Arthroscopy: J Arthroscopic & Related Surg 2015: 31(3): pp 561-568). Asthe article concludes, “The major findings of this study were prolongedknee effusion, increased femoral tunnel widening, and increased screwbreakage associated with Bioabsorbable Interference Screw use”.

On a mechanical level, higher percentage level of mineral composition ina biocomposite implant can lead to poor mechanical results andspecifically mechanical results that are inferior to the mechanicalresults of implants comprised solely of bioabsorbable polymer. Forexample, the effect of different percentages of beta-tricalciumphosphate (βTCP) on the mechanical properties of a PLA basedbiocomposite have been studied (Ferri J M et al. J Composite Materials.2016; 0(0): 1-10).

In that study, it was shown that higher percentages of βTCP result in asignificant loss of tensile strength for the PLA-βTCP biocomposite,shown in FIG. 1 of that reference.

Furthermore, an increase in the percentage of βTCP results in asignificant loss in the amount of energy the biocomposite can absorb, asmeasured as Charpy's impact energy. This is a very important parameterin orthopedic implants since a key property of an orthopedic implant isthe ability to withstand impact without fracturing. Table 2 (taken fromthe above reference) demonstrates this problem.

TABLE 2 Shore D hardness values and Charpy's absorbed energy ofPLA/β-TCP composites in terms of the β-TCP weight percent. Shore DCharpy's impact Wt % β-TCP hardness energy (J/m²) 0 71 ± 1 1.85 ± 0.2 1074 ± 1 1.68 ± 0.3 20 75 ± 1 1.40 ± 0.2 30 77 ± 1 1.25 ± 0.1 40 79 ± 11.10 ± 0.2

SUMMARY OF THE INVENTION

There is a great need for a reinforced bioabsorbable polymer materialexhibiting improved mechanical properties for use in load-bearingmedical implant applications, such as structural fixation forload-bearing purposes, where the high strength and stiffness of theimplant are retained at a level equivalent to or exceeding cortical bonefor a period at least as long as the maximum bone healing time.

The construction of biocomposite fiber-reinforced materials with therequisite high strength and stiffness is known in the art to be adifficult problem, which so far has not been provided with an adequatesolution.

Specifically within such fiber-reinforced composites, achieving the highstrengths and stiffness required for many medical implant applicationscan require the use of fiber reinforcement with a high mineral contentpercentage comprised of either continuous fibers or short or long fiberreinforcement. This creates a significant difference from the implantstructures, architectures, designs, and production techniques that havebeen previously used with medical implants produced from polymers orcomposites comprising lower mineral content particle or short fiberreinforced polymers. Those implants are most commonly produced usinginjection molding, or occasionally 3-D printing, production techniques.

Unlike with bulk materials, the properties of parts made from compositematerials are highly dependent on the internal structure of the part.This is a well-established principle in the design of parts fromcomposite materials where the mechanical properties of fiber-reinforcedcomposite materials are known to be dependent on the angles andorientations of the fibers within the composite parts.

The vast majority of prior composite material part design focusedexclusively on the mechanical properties of the parts. However, theseparts were permanent parts and not degradable or absorbable. Therefore,no attention had to be given to the mechanisms of degradation orabsorption of the composite materials within the part. Even previousorthopedic implants comprised of composite materials have largelyadhered to these same classical composite material design principles.

However, the herein invention relates to medical implants comprised of anew class of composite materials that are biocompatible and in manycases are bioabsorbable. The design challenges in creating medicalimplants with these materials involve consideration of many more aspectsand parameters than just the mechanical properties that have previouslybeen considered with composite material parts.

Furthermore, with regard to bioabsorbable fiber-reinforced compositeimplants, the degradation profile of the composite material within theimplant must also be taken into consideration in ensuring that thefibers will provide strength and stiffness reinforcement both initiallyat the initial time of device implantation and also over the course ofits functional period within the body.

Mechanical properties that are critical to the performance of medicalimplants in the herein invention include: flexural, tensional, shear,compressional, and torsional strength and stiffness (modulus). In thesebioabsorbable medical implants, these properties are critical both attime zero (i.e. in the implant following production) and following aperiod of implantation in the body. As with previously described partsmade from fiber-reinforced composite material, the mechanical propertiesat time zero are dependent on the alignment and orientation of fiberswithin the part. However, retaining a large percentage of the mechanicalproperties following implantation in the body (or simulatedimplantation) requires additional and different considerations.

As will be described in more detail below, such considerations for themedical implant design can include the following parameters:compositions, component ratios (including specifically mineral contentpercentage), fiber diameters, fiber distribution, fiber length, fiberalignments and orientations, etc.

These parameters can impact several additional aspects and properties ofthe herein described medical implant performance:

1. Material degradation rate (degradation products, local pH and ionlevels during degradation)

2. Surface properties that affect interface of implant with surroundinglocal tissue

3. Biological effects such as anti-microbial or osteoconductiveproperties

4. Response to sterilization processes (such as ethylene oxide gas,gamma or E-beam radiation)

The present invention provides a solution to these problems byproviding, in at least some embodiments, implant compositions from fiberreinforced biocompatible composite materials that are a significant stepforward from previous implants in that they can achieve sustainablyhigh, load bearing strengths and stiffness. Additionally, manyembodiments of the present invention additionally facilitate these highstrength levels with efficient implants of low volume. Furthermore, thebiocomposite materials described herein are also optionally andpreferably bioabsorbable.

The present invention therefore overcomes the limitations of previousapproaches and provides medical implants comprising (optionallybiodegradable) biocomposite compositions featuring fiber-reinforcementthat retain their mechanical strength and stiffness for an extendedperiod.

The present invention, in at least some embodiments, further overcomesthe limitations of previous biocomposite medical implants by providingmedical implants comprised of a biocomposite material composition with ahigh percentage of mineral content and yet with superior mechanicalproperties. Preferably the mineral composition is provided by areinforcing fiber made from the mineral composition.

Preferably, the weight percentage of the mineral composition within thebiocomposite medical implant is in the range of 40-90%, more preferablythe weight percentage is in the range of 40%-70%, more preferably in therange of 40%-65%, and even more preferably the weight percentage is inthe range of 45%-60%.

Surprisingly, the inventors have found that such a high percentage oramount of mineral content can yield implants with superior mechanicalproperties.

Additionally, previous attempts to construct implants with highermineral contents failed because biocomposite implants are typicallyinjection molded. The flow properties of a composite with an amount orpercentage of mineral content in the above high range are morechallenging to injection mold.

These preferential ranges derive from a critical balance betweenbiocompatibility (quiescent inflammatory response) and strong mechanicalproperties. As discussed previously, higher mineral content percentagein the medical implant has potential beneficial in increasingbiocompatibility and safety profile of the implant with the surroundingtissues, especially bony tissues. However, mineral content that is toohigh can result in an undesirable reduction in mechanical properties. Insome cases a reduction in implant mechanical properties will be seenimmediately. In other cases, high mineral content can result in anaccelerated mechanical degradation process wherein the implant will loseits mechanical properties at an accelerated rate and thereby lose itsability to provide mechanical fixation for an in vivo time periodsufficient to support tissue (and especially orthopedic tissue) healing.

Preferably the density of the biocomposite composition for use in hereininvention is between 1 to 2 g/mL. More preferentially, density isbetween 1.2 to 1.9 g/mL. Most preferentially between 1.4 to 1.8 g/mL.

Preferably, the mineral content is provided by a reinforcing mineralfiber made from the mineral composition.

Optionally, the diameter of reinforcing fiber for use with hereinreinforced biocomposite medical implant can be in the range of 1-100 μm.Preferably, fiber diameter is in the range of 1-20 μm. More preferably,fiber diameter is in the range of 4-16 μm, and most preferably in therange of 9-14 μm.

The standard deviation of fiber diameter between fibers within themedical implant is preferably less than 5 μm, more preferably less than3 μm, and most preferably less than 1.5 μm. Uniformity of fiber diameteris beneficial for consistent properties throughout the implant.

In one embodiment, reinforcing fibers are fiber segments inside thepolymer matrix. Preferably such fiber segments are, on average, oflength 0.5-20 mm, more preferably the fiber segment length is in therange of 1-15 mm, more preferably in the range of 3-10 and mostpreferably in the range of 4-8 mm.

Optionally and preferably the above mineral composition is provided inthe form of a reinforcing fiber, present in a sufficiently high amountand with a sufficiently high mineral quantity to provide the aboveweight percentage of the mineral composition within the implant.

The overall structure of the implant may optionally be heterogeneousand/or amorphous. If heterogeneous, the structure may optionally becontinuous in its properties. Alternatively, the implant may optionallybe divided into layers.

According to at least some embodiments, there is provided a medicalimplant comprising a plurality of biocomposite layers, said layerscomprising a polymer, which is optionally biodegradable, and a pluralityof uni-directionally aligned continuous reinforcement fibers. The layersmay optionally be amorphous or aligned. Optionally and preferably, thebiodegradable polymer is embodied in a biodegradable composite. Alsooptionally and preferably, the fibers are embedded in a polymer matrixcomprising one or more bioabsorbable polymers.

According to at least some embodiments, the composite layers are eachcomprised of one or more composite tapes, said tape comprising apolymer, which is optionally biodegradable, and a plurality ofuni-directionally aligned continuous reinforcement fibers. Optionallyand preferably, the biodegradable polymer is embodied in a biodegradablecomposite. Also optionally and preferably, the fibers are embedded in apolymer matrix comprising one or more bioabsorbable polymers.

Optionally and preferably, the fiber-reinforced biodegradable compositewithin the implant has a flexural modulus exceeding 5 GPa and flexuralstrength exceeding 80 MPa.

Preferably, the fiber-reinforced biodegradable composite within theimplant has flexural strength in range of 150-800 MPa, more preferably150-400 MPa. Elastic modulus is preferably in range of 5-27 GPa, morepreferably 16-27 GPa.

Preferably, the fiber-reinforced composite within the implant hasstrength retention of Elastic Modulus above 5 GPa after 8 weeksimplantation and flexural strength above 60 MPa after 8 weeks.

Preferably, the fiber-reinforced composite within the implant hasmechanical property retention of Flexural Modulus above 12 GPa andflexural strength above 180 MPa after 5 days of simulated physiologicaldegradation.

More preferably, the fiber-reinforced composite within the implant hasmechanical property retention of Flexural Modulus above 10 GPa andflexural strength above 120 MPa after 5 days of simulated physiologicaldegradation.

The term “biodegradable” as used herein also refers to materials thatare resorbable, bioabsorbable or absorbable in the body.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 2,500×. This image shows a magnification of the crosssection of reinforcing mineral fibers 102 embedded within bioabsorbablepolymer matrix 104. The fiber diameter is indicated within the image106.

FIG. 2: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 2,500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix. The distance between adjacent fibers is indicated by202.

FIG. 3: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix. Each layer 306 308 310 is comprised of reinforcementfibers 304 and is of a certain thickness 302.

FIG. 4: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 150×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix.

FIG. 5: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix. Each layer is separated by an area of bioabsorbablepolymer matrix 502.

FIG. 6: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 70% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix. The distance between adjacent fibers is indicated.

FIG. 7: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 70% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix.

FIG. 8: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 2,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The fiber diameter is indicated within theimage.

FIG. 9: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 2,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The distance between adjacent fibers isindicated.

FIG. 10: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix.

FIG. 11: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 5,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers 1102 embedded withinbioabsorbable polymer matrix 1104.

FIG. 12: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au Sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. Each layer is separated by an area ofbioabsorbable polymer matrix.

FIG. 13: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au Sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The fiber diameter is indicated within theimage.

FIG. 14: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au Sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The distance between adjacent fibers isindicated.

FIG. 15: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix.

FIG. 16: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au Sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. Each layer is separated by an area ofbioabsorbable polymer matrix.

FIG. 17: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 50%fiber content by weight, such as those described in Example 3.Magnification of this image is 1250×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The fiber diameter is indicated within theimage.

FIG. 18: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 50%fiber content by weight, such as those described in Example 3.Magnification of this image is 1250×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The distance between adjacent fibers isindicated.

FIG. 19: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 70%fiber content by weight, such as those described in Example 3.Magnification of this image is 250×. This image shows a magnification ofthe cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. Each layer 1902, 1904 is comprised offibers. The distance between adjacent fibers is indicated.

FIG. 20: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 70%fiber content by weight, such as those described in Example 3.Magnification of this image is 250×. This image shows a magnification ofthe cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix.

FIG. 21: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 70%fiber content by weight, such as those described in Example 3.Magnification of this image is 500×. This image shows a magnification ofthe cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. Each layer is separated by an area ofbioabsorbable polymer matrix.

FIG. 22: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 300×. This image shows a magnification ofthe longitudinal axis of reinforcing mineral fibers 2202.

FIG. 23: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 250×. This image shows a magnification ofthe cannulated portion and the continuous, reinforcing mineral fibers.The tangential angle 2302 is defined as the deviation from the directionof the curve at a fixed starting point, where the fixed starting pointis the point where the fiber touches or is closest to coming intocontact with the center of the cross-sectional circular area.

FIG. 24: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 6 mm pin with 50%fiber content by weight, such as those described in Example 1.Magnification of this image is 500×. This image shows a magnification ofthe cross section of reinforcing mineral fibers, bundled tightlytogether in groups 2402 embedded within bioabsorbable polymer matrix.

FIG. 25: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 500×. This image shows a magnification ofthe cross section of reinforcing mineral fibers surrounding the innercannulation of the pin 2502.

FIG. 26: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1000×. This image shows a magnificationof the cross section of reinforcing mineral fibers, embedded withinbioabsorbable polymer matrix layers in alternating 0° and 45°orientation.

FIG. 27: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 6 mm pin with 85%fiber content by weight, such as those described in Example 1.Magnification 160×. This image shows a magnification of the crosssection of reinforcing mineral fibers, embedded within layers 2702 inalternating 0° and 45° orientation, with little or no bioabsorbablepolymer matrix separating the layers.

FIG. 28: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 6 mm pin with 85%fiber content by weight, such as those described in Example 1.Magnification 1000×. This image shows a magnification of the crosssection of reinforcing mineral fibers, with little or no bioabsorbablepolymer matrix surrounding the said fibers.

FIG. 29: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm pin with 50% fibercontent by weight, such as those described in Example 2. Magnification60×. This image shows a magnification of the edge of the pin, indicatingthat the bioabsorbable polymer is present at the outer surface of theimplant 2902.

FIG. 30 shows an example of a continuous fiber-reinforced tape of thetype that can be used to form a layer in a medical implant comprised ofcontinuous fiber-reinforced layers.

FIG. 31 shows an example of a cut-away, three-dimensional view of acontinuous fiber-reinforced tape (200).

FIG. 32a shows an example of a top-view of a reinforced bioabsorbablecomposite sheet (300) comprised of three layers of uni-directionalfibers at different angles.

FIG. 32b shows an example of a cut-away view of a reinforcedbioabsorbable composite structure (310) comprised of three layers ofuni-directional fibers at different angles.

FIG. 33 shows an example of the wall of a continuous-fiber reinforcedcomposite medical implant.

FIG. 34 shows an example of a bone filler cage that consists ofcontinuous-fiber reinforced composite medical implant walls (500) thatadditionally contains perforations (502) to allow tissue and cellularingrowth into the bone filler material (504) contained within the bonefiller cage.

FIG. 35 shows an example of a bioabsorbable cannulated screw (600) thatis a medical implant.

DETAILED DESCRIPTION

A medical implant according to at least some embodiments of the presentinvention is suitable for load-bearing orthopedic implant applicationsand comprises one or more biocomposite, optionally bioabsorbable,materials where sustained mechanical strength and stiffness are criticalfor proper implant function and wherein the implant is additionallycomprised of a moisture barrier coating that restricts or eliminatesfluid exchange into the implant.

The present invention, according to at least some embodiments, thusprovides medical implants that are useful as structural fixation forload-bearing purposes, exhibiting sustained mechanical properties as aresult of impeded degradation of the bioabsorbable materials thatcomprise the implant.

Relevant implants may include bone fixation plates, intramedullarynails, joint (hip, knee, elbow) implants, spine implants, sutureanchors, screws, pins, wires, bone cages, and other devices for suchapplications such as for fracture fixation, tendon reattachment, spinalfixation, soft tissue repair, and spinal cages.

According to at least some embodiments, the herein invention relates tomedical implants comprised of a biocomposite material composition.Preferably the biocomposite material composition is comprised of (anoptionally bioabsorbable) polymer reinforced by a mineral composition.Preferably the mineral composition reinforcement is provided by areinforcing fiber made from the mineral composition. As described above,the mineral content of the implant is preferably quite high.

Optionally, the medical implant or part thereof is comprised of a numberof biocomposite layers, each layer comprising bioabsorbable polymerreinforced by uni-directional reinforcing fibers. The properties of theimplant are optionally and preferably determined according to the layercomposition and structure, and the placement of the layers in regard tothe device, for example with regard to layer direction. The fibers mayoptionally remain discrete but optionally some melting of the polymermay occur to bind the layers together.

A biocomposite layer can be defined as a continuous or semi-continuousstratum running through part or all of a medical implant, wherein thelayer is comprised of reinforcing fibers that aligned uni-directionally.Layers can be seen in several figures showing the internal structure ofreinforced biocomposite medical implants, including in FIGS. 7, 10, and20.

Preferably, there are between 1-100 reinforcing fibers forming thethickness of each biocomposite layer. Preferably, there are between 2-40reinforcing fibers in each layer thickness and most preferably there arebetween 4-20 reinforcing fibers.

Optionally, the directional fiber orientation between adjacent layerswithin the implant alternates between layers such that each adjacentlayer is out of phase (of a different angle) from the layer that isadjacent to it. Preferably, the average or median angle differencebetween layers is between 15 to 75 degrees, more preferably between 30to 60 degrees, and most preferably between 40 to 50 degrees. Microscopicimages of such out of phase adjacent biocomposite layers can be seen inFIGS. 26 and 27.

Preferably, the biocomposite layers within the medical implant are wellapproximated to each other. More preferably, the distance betweenlayers, as measured by the distance between the last fiber in one layersand the first fiber in the subsequent layer is between 0-200 μm, morepreferably between 0-60 μm, 1-40 μm, and most preferably between 2-30μm. Good approximation of the fibers within a layer to the fibers withinthe adjacent layer allow each layer to mechanically support the adjacentlayer. However, some distance between the layers may be desirable toallow for some polymer to remain between the fibers of adjacent layersand thus adhere the layers together, prevent layer dehiscence under highmechanical load.

Optionally, the diameter of a majority of reinforcing fiber for use withherein reinforced biocomposite medical implant is in the range of 1-100μm. Preferably, fiber diameter is in the range of 1-20 μm. Morepreferably, fiber diameter is in the range of 4-16 μm, and mostpreferably in the range of 9-14 μm.

Optionally, the average diameter of reinforcing fiber for use withherein reinforced biocomposite medical implant is in the range of 1-100μm. Preferably, fiber diameter is in the range of 1-20 μm. Morepreferably, fiber diameter is in the range of 4-16 μm, and mostpreferably in the range of 9-14 μm.

The standard deviation of fiber diameter between fibers within themedical implant is preferably less than 5 μm, more preferably less than3 μm, and most preferably less than 1.5 μm. Uniformity of fiber diameteris beneficial for consistent properties throughout the implant.

In one embodiment, reinforcing fibers are fiber segments inside thepolymer matrix. Preferably such fiber segments are, on average, oflength 0.5-20 mm, more preferably the fiber segment length is in therange of 1-15 mm, more preferably in the range of 3-10 and mostpreferably in the range of 4-8 mm.

Preferably, a majority of reinforcing fiber segments are of length0.5-20 mm, more preferably the fiber segment length is in the range of1-15 mm, more preferably in the range of 3-10 and most preferably in therange of 4-8 mm.

Optionally, the reinforcing fibers are continuous fibers. Saidcontinuous fibers are preferably longer than 5 mm, more preferablylonger than 8 mm, 12 mm, 16 mm, and most preferably longer than 20 mm. Amicroscopic image of such continuous fibers can be seen in FIG. 22.

Alternatively, or in addition, the reinforcing fiber length can bedefined as a function of implant length wherein at least a portion ofthe reinforcing fibers, and preferably a majority of the reinforcingfibers, are of a continuous length at least 50% the longitudinal lengthof the medical implant or medical implant component that is comprised ofthese fibers. Preferably, the portion or majority of the reinforcingfibers are of continuous length at least 60% of the length of themedical implant, and more preferably at least 75% of the length of themedical implant. Such continuous reinforcing fibers can providestructural reinforcement to a large part of the implant.

Optionally, the distance between adjacent reinforcing fibers within abiocomposite layer is in the range of 0.5-50 μm, preferably the distancebetween adjacent fibers is in the range of 1-30 μm, more preferably inthe range of 1-20 μm, and most preferably in the range of 1-10 μm.

Preferably, the weight percentage of the reinforcing fibers (mineralcomposition) within the biocomposite medical implant is in the range of40-90%, more preferably the weight percentage is in the range of40%-70%, more preferably in the range of 40%-60%, and even morepreferably the weight percentage is in the range of 45%-60%.

Preferably, the volume percentage of reinforcing fibers within thebiocomposite medical implant is in the range of 30-90%, more preferablythe volume percentage is in the range of 40%-70%.

Optionally, a plurality of fibers within the implant areuni-directionally aligned. Optionally, the aligned fiber segments are,on average, of length 5-12 mm.

Preferably, the uni-directionally aligned fibers are aligned in thelongitudinal access of the implant (0° alignments in relation to thelongitudinal axis). Preferably, a majority of fibers areuni-directionally aligned in the longitudinal axis. Optionally, morethan 70%, 80%, 90%, 95% of fibers are uni-directionally aligned in thelongitudinal axis.

Optionally, a plurality or a majority of fibers within the implant arealigned in the longitudinal axis. Optionally, a plurality of fibers areadditionally aligned in up to 3 additional directions. Optionally, aplurality of fibers are aligned in a selection of each of the followingalignments in relation to the longitudinal axis: 0°, 30°, −30°, 45°,−45°, 90°. Preferably, a plurality of fibers are aligned in a selectionof each of the following alignments in relation to the longitudinalaxis: 0°, 45°, −45°, 90°. More preferably, a plurality of fibers arealigned in a selection of each of the following alignments in relationto the longitudinal axis: 0°, 45°, −45°.

Optionally, a majority of fibers are aligned in the longitudinal accessof the implant and a plurality of fibers are aligned in each of thefollowing alignments in relation to the longitudinal axis: 45°, −45°.

Optionally and alternatively, fiber segments are arranged amorphously.

While the biocomposite composition within the implant is important indetermining the mechanical and bulk properties of the implant, thespecific composition and structure that comes into contact with thesurface edge of the implant has unique significance in that thiscomposition and structure can greatly affect how surrounding cells andtissue interact with the implant following implantation into the body.For example, the absorbable polymer part of the biocomposite may behydrophobic in nature such that it will repel surrounding tissues to acertain degree while the mineral reinforcing fiber part of thebiocomposite may be hydrophilic in nature and therefore encouragesurrounding tissues to attach to the implant or create tissue ingrowth.

In an optional embodiment of the herein invention, the surface presenceof one of the compositional components by percentage of surface area isgreater than the presence of that component in the bulk composition ofthe implant by volume percentage. For example, the amount of mineral onthe surface might be greater than the amount of polymer, or vice versa.Without wishing to be limited by a single hypothesis, for greaterintegration with bone, a greater amount of mineral would optionally andpreferably be present on the surface. For reduced integration with bone,a greater amount of polymer would optionally and preferably be presenton the surface. Preferably, the percentage of surface area compositionof one component is more than 10% greater than the percentage of volumepercentage of that component in the overall biocomposite implant. Morepreferably, the percentage is more than 30% greater, and most preferablymore than 50% greater. FIG. 25 shows a microscopic image of abiocomposite medical implant with a predominance of mineral reinforcingfiber along the inner surface area edge of the implant. FIG. 29 shows amicroscopic image of a biocomposite medical implant with a predominanceof bioabsorbable polymer along the outer surface area of the implant.

Optionally, one surface of the medical implant may have a localpredominance of one of the biocomposite components while a differentsurface, or different part of the same surface, may have a localpredominance of a different biocomposite component

Optionally, mineral content is not present in a majority of the surfacearea (i.e. a majority of the surface of the implant is covered with apolymer film). Optionally, the surface polymer film is, on average,0.5-50 μm in thickness, more preferably 5-50 μm and most preferably10-40 μm.

Optionally, there are fibers exposed at the surface of the implant.Optionally, exposed fibers comprise 1-60% of implant surface.Optionally, exposed fibers comprise 10-50% of implant surface.Optinally, exposed fibers comprise 15-30% of implant surface.

Optionally, the medical implant is a threaded screw or other threadedimplant. Preferably, the outer layer of the implant will bedirectionally aligned such that the direction of the fibers approximatesthe helix angle of the threading. Preferably, the alignment angle of thefiber direction is within 45 degrees of the helix angle. Morepreferably, the alignment angle is within 30 degrees, and mostpreferably the alignment angle is within 15 degrees of the helix angle.Approximating the fiber alignment angle to the helix angle in thismanner can improve the robustness of the threading and preventdehiscence of the reinforcing fibers within the threading.

With regard to circular implants, the reinforcing fibers may optionallytake the full circular shape of the implant and curve around the circleshape of the implant without deviation from its circumference.Preferably, a portion or a majority of the reinforcing fibers deviatefrom the circle shape of the implant such that a tangential angle isformed. The tangential angle is defined as the deviation from thedirection of the curve at a fixed starting point, where the fixedstarting point is the point where the fiber touches or is closest tocoming into contact with the center of the cross-sectional circulararea. FIG. 23 depicts the tangential angle of reinforcing fibers to acannulated circular pin.

Preferably the tangential angle between reinforcing fibers within thecircular medical implant and the curvature of the implant is less than90 degrees, more preferably less than 45 degrees.

Preferably the density of the biocomposite composition for use in hereininvention is between 1 to 2 g/mL. More preferentially, density isbetween 1.2 to 1.9 g/mL. Most preferentially between 1.4 to 1.8 g/mL.

Bioabsorbable Polymers

In a preferred embodiment of the present invention, the biodegradablecomposite comprises a bioabsorbable polymer.

The medical implant described herein may be made from any biodegradablepolymer. The biodegradable polymer may be a homopolymer or a copolymer,including random copolymer, block copolymer, or graft copolymer. Thebiodegradable polymer may be a linear polymer, a branched polymer, or adendrimer. The biodegradable polymers may be of natural or syntheticorigin. Examples of suitable biodegradable polymers include, but are notlimited to polymers such as those made from lactide, glycolide,caprolactone, valerolactone, carbonates (e.g., trimethylene carbonate,tetramethylene carbonate, and the like), dioxanones (e.g.,1,4-dioxanone), 6-valerolactone, 1,dioxepanones) e.g.,1,4-dioxepan-2-one and 1,5-dioxepan-2-one), ethylene glycol, ethyleneoxide, esteramides, γ-ydroxyvalerate, β-hydroxypropionate, alpha-hydroxyacid, hydroxybuterates, poly (ortho esters), hydroxy alkanoates,tyrosine carbonates, polyimide carbonates, polyimino carbonates such aspoly (bisphenol A-iminocarbonate) and poly (hydroquinone-iminocarbonate,(polyurethanes, polyanhydrides, polymer drugs (e.g., polydiflunisol,polyaspirin, and protein therapeutics (and copolymers and combinationsthereof. Suitable natural biodegradable polymers include those made fromcollagen, chitin, chitosan, cellulose, poly (amino acids),polysaccharides, hyaluronic acid, gut, copolymers and derivatives andcombinations thereof.

According to the present invention, the biodegradable polymer may be acopolymer or terpolymer, for example: polylactides (PLA), poly-L-lactide(PLLA), poly-DL-lactide (PDLLA); polyglycolide (PGA); copolymers ofglycolide, glycolide/trimethylene carbonate copolymers (PGA/TMC); othercopolymers of PLA, such as lactide/tetramethylglycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/d-valerolactonecopolymers, lactide/ε-caprolactone copolymers, L-lactide/DL-lactidecopolymers, glycolide/L-lactide copolymers (PGA/PLLA),polylactide-co-glycolide; terpolymers of PLA, such aslactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolide/ε-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically-3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates; such aspolyhydroxybutyrates (PHB); PHB/b-hydroxyvalerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone-poly-ε-capralactone,poly(ε-caprolactone-DL-lactide) copolymers; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinylalcohol (PVA); polypeptides; poly-b-malic acid (PMLA):poly-b-alkanbic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides); and mixtures thereof; and natural polymers, suchas sugars; starch, cellulose and cellulose derivatives, polysaccharides,collagen, chitosan, fibrin, hyalyronic acid, polypeptides and proteins.Mixtures of any of the above-mentioned polymers and their various formsmay also be used.

Reinforced Bioabsorbable Polymers

According to at least some embodiments of the present invention, themedical implant comprises a reinforced bioabsorbable polymer (i.e. abioabsorbable composite that includes the previously described polymerand also incorporates a reinforcing filler, generally in fiber form, toincrease the mechanical strength of the polymer).

In a more preferred embodiment of the present invention, the reinforcedbioabsorbable polymer is a reinforced polymer composition comprised ofany of the above-mentioned bioabsorbable polymers and a reinforcingfiller, preferably in fiber form. The reinforcing filler may becomprised of organic or inorganic (that is, natural or synthetic)material. Reinforcing filler may be a biodegradable glass, a cellulosicmaterial, a nano-diamond, or any other filler known in the art toincrease the mechanical properties of a bioabsorbable polymer. Thefiller is preferably made from a material or class of material otherthan the bioabsorbable polymer itself. However, it may also optionallybe a fiber of a bioabsorbable polymer itself.

Numerous examples of such reinforced polymer compositions havepreviously been documented. For example: A biocompatible and resorbablemelt derived glass composition where glass fibers can be embedded in acontinuous polymer matrix (EP 2 243 749 A1), Biodegradable compositecomprising a biodegradable polymer and 20-70 vol % glass fibers(WO2010128039 A1), Resorbable and biocompatible fiber glass that can beembedded in polymer matrix (US 2012/0040002 A1), Biocompatible compositeand its use (US 2012/0040015 A1), Absorbable polymer containingpoly[succinimide] as a filler (EPO 671 177 B1).

In a more preferred embodiment of the present invention, the reinforcingfiller is bound to the bioabsorbable polymer such that the reinforcingeffect is maintained for an extended period. Such an approach has beendescribed in US 2012/0040002 A1 and EP 2243500B1, which discusses acomposite material comprising biocompatible glass, a biocompatiblematrix polymer and a coupling agent capable of forming covalent bonds.

As noted above, the biodegradable composite and fibers are preferablyarranged in the form of biodegradable composite layers, where each layercomprises uni-directionally aligned continuous reinforcement fibersembedded in a polymer matrix comprised of one or more bioabsorbablepolymers.

The biodegradable composite layers are preferably comprised of one ormore biodegradable composite tapes, where each tape comprisesuni-directionally aligned continuous reinforcement fibers embedded in apolymer matrix comprised of one or more bioabsorbable polymers.

The biodegradable composite is preferably embodied in a polymer matrix,which may optionally comprise any of the above polymers. Optionally andpreferably, it may comprise a polymer selected from the group consistingof PLLA (poly-L-lactide), PDLLA (poly-DL-lactide), PLDLA, PGA(poly-glycolic acid), PLGA (poly-lactide-glycolic acid), PCL(Polycaprolactone), PLLA-PCL and a combination thereof. If PLLA is used,the matrix preferably comprises at least 30% PLLA, more preferably 50%,and most preferably at least 70% PLLA. If PDLA is used, the matrixpreferably comprises at least 5% PDLA, more preferably at least 10%,most preferably at least 20% PDLA.

Preferably, the inherent viscosity (IV) of the polymer matrix(independent of the reinforcement fiber) is in the range of 1.2 to 2.4dl/g, more preferably in the range of 1.5 to 2.1 dl/g, and mostpreferably in the range of 1.7 to 1.9 dl/g.

Inherent Viscosity (IV) is a viscometric method for measuring molecularsize. IV is based on the flow time of a polymer solution through anarrow capillary relative to the flow time of the pure solvent throughthe capillary.

Reinforcement Fiber

Preferably, reinforcement fiber is comprised of silica-based mineralcompound such that reinforcement fiber comprises a bioresorbable glassfiber, which can also be termed a bioglass fiber composite.

Mineral composition may include beta-tricalcium phosphate, calciumphosphate, calcium sulfate, hydroxyapatite, or a bioresorbable glass(also known as bioglass).

Additional optional glass fiber compositions have been describedpreviously by Lehtonen T J et al. (Acta Biomaterialia 9 (2013)4868-4877), which is included here by reference in its entirety; suchglass fiber compositions may optionally be used in place of or inaddition to the above compositions.

Additional optional bioresorbable glass compositions are described inthe following patent applications, which are hereby incorporated byreference as if fully set forth herein: Biocompatible composite and itsuse (WO2010122098); and Resorbable and biocompatible fibre glasscompositions and their uses (WO2010122019).

In a more preferred embodiment of the present invention, the reinforcingfiller is bound to the bioabsorbable polymer such that the reinforcingeffect is maintained for an extended period. Such an approach has beendescribed in US 2012/0040002 A1 and EP 2243500B1, which discusses acomposite material comprising biocompatible glass, a biocompatiblematrix polymer and a coupling agent capable of forming covalent bonds.

Bioresorbable glass fiber may optionally have oxide compositions in thefollowing mol. % ranges:

Na₂O: 11.0-19.0 mol. %

CaO: 9.0-14.0 mol. %

MgO: 1.5-8.0 mol. %

B₂O₃: 0.5-3.0 mol. %

Al₂O₃: 0-0.8 mol. %

P₂O₃: 0.1-0.8 mol. %

SiO₂: 67-73 mol. %

And more preferably in the following mol. % ranges:

Na₂O: 12.0-13.0 mol. %

CaO: 9.0-10.0 mol. %

MgO: 7.0-8.0 mol. %

B₂O₃: 1.4-2.0 mol. %

P₂O₃: 0.5-0.8 mol. %

SiO₂: 68-70 mol. %

Additional optional glass fiber compositions have been describedpreviously by Lehtonen T J et al. (Acta Biomaterialia 9 (2013)4868-4877), which is included here by reference in its entirety; suchglass fiber compositions may optionally be used in place of or inaddition to the above compositions.

Additional optional bioresorbable glass compositions are described inthe following patent applications, which are hereby incorporated byreference as if fully set forth herein: Biocompatible composite and itsuse (WO2010122098); and Resorbable and biocompatible fibre glasscompositions and their uses (WO2010122019).

Optional Additional Features

The below features and embodiments may optionally be combined with anyof the above features and embodiments.

Tensile strength of the reinforcement fiber is preferably in the rangeof 1200-2800 MPa, more preferably in the range of 1600-2400 MPa, andmost preferably in the range of 1800-2200 MPa.

Elastic modulus of the reinforcement fiber is preferably in the range of30-100 GPa, more preferably in the range of 50-80 GPa, and mostpreferably in the range of 60-70 GPa.

Fiber diameter is preferably in the range of 6-20 μm, more preferably inthe range of 10-18 μm, and most preferably in the range of 14-16 μm.

Optionally, a majority of reinforcement fibers aligned to thelongitudinal axis of the medical implant are of a length of at least 50%of the total length of the implant, preferably at least 60%, morepreferably at least 75%, and most preferably at least 85%.

Optionally, fibers may be aligned at an angle to the longitudinal axis(i.e. on a diagonal) such that the length of the fiber may be greaterthan 100% of the length of the implant. Optionally and preferably, amajority of reinforcement fibers are aligned at an angle that is lessthan 90°, alternatively less than 60°, or optionally less than 45° fromthe longitudinal axis.

Preferably, the implant preferably comprises between 2-20 composite tapelayers, more preferably between 2-10 layers, and most preferably between2-6 layers; wherein each layer may be aligned in a different directionor some of the layers may be aligned in the same direction as the otherlayers.

Preferably, the maximum angle between fibers in at least some of thelayers is greater than the angle between the fibers in each layer andthe longitudinal axis. For example, one layer of reinforcing fibers maybe aligned and a right diagonal to the longitudinal axis while anotherlayer may be aligned at a left diagonal to the longitudinal axis.

Compatibilizer

Optionally and preferably, the composite composition additionallyincludes a compatibilizer, which for example be such an agent asdescribed in WO2010122098, hereby incorporated by reference as if fullyset forth herein.

Biodegradable Composite Alternative Forms

Alternatively, biodegradable composite may comprise composite strandscomprising continuous reinforcement fibers or fiber bundles impregnatedwith bioabsorbable polymer. Preferably, strands are less than 1 cm indiameter. More preferably, strands are less than 8 mm, less than 5 mm,less than 3 mm, or less than 2 mm in diameter.

Alternatively, biodegradable composite may comprise a woven mesh ofcontinuous reinforcement fibers wherein woven mesh is pre-impregnatedwith bioabsorbable polymer or woven mesh is comprised of reinforcementfibers and subsequently impregnated with bioabsorbable polymer.

Preferably, biodegradable composite mesh layer is less than 1 cm inthickness. More preferably, impregnated mesh is less than 8 mm, lessthan 5 mm, less than 3 mm, or less than 2 mm in thickness.

Mineral Content

The present invention, in at least some embodiments, further overcomesthe limitations of previous biocomposite medical implants by providingmedical implants comprised of a biocomposite material composition with ahigh percentage of mineral content and yet with superior mechanicalproperties. Preferably the mineral composition is provided by areinforcing fiber made from the mineral composition.

Preferably, the weight percentage of the mineral composition within thebiocomposite medical implant is in the range of 40-90%, more preferablythe weight percentage is in the range of 40%-70%, and even morepreferably the weight percentage is in the range of 45%-60%.

Preferably the density of the biocomposite composition for use inpresent invention, in at least some embodiments, is between 1 to 2 g/mL.More preferentially, density is between 1.2 to 1.9 g/mL. Mostpreferentially density is between 1.4 to 1.8 g/mL.

The diameter of reinforcing fiber for use with the reinforcedbiocomposite medical implant can be in the range of 1-100 μm.Preferably, fiber diameter is in the range of 1-20 μm. More preferably,fiber diameter is in the range of 4-16 μm.

The standard deviation of fiber diameter between fibers within themedical implant is preferably less than 5 μm, more preferably less than3 μm, and most preferably less than 1.5 μm. Uniformity of fiber diameteris beneficial for consistent properties throughout the implant.

Optionally and preferably, the fiber-reinforced biodegradable compositewithin the implant has a flexural modulus exceeding 5 GPa and flexuralstrength exceeding 80 MPa.

Preferably, the fiber-reinforced biodegradable composite within theimplant has flexural strength in range of 150-800 MPa, more preferably150-400 MPa. Elastic modulus is preferably in range of 5-27 GPa, morepreferably 10-27 GPa.

Preferably, the fiber-reinforced composite within the implant hasstrength retention of Elastic Modulus above 10 GPa after 8 weeksimplantation and flexural strength above 150 MPa after 8 weeks.

According to the present invention, in at least some embodiments, thebiodegradable polymer may be a copolymer or terpolymer, for example:polylactides (PLA), poly-L-lactide (PLLA), poly-DL-lactide (PDLLA);polyglycolide (PGA); copolymers of glycolide, glycolide/trimethylenecarbonate copolymers (PGA/TMC); other copolymers of PLA, such aslactide/tetramethylglycolide copolymers, lactide/trimethylene carbonatecopolymers, lactide/d-valerolactone copolymers, lactide/ε-caprolactonecopolymers, L-lactide/DL-lactide copolymers, glycolide/L-lactidecopolymers (PGA/PLLA), polylactide-co-glycolide; terpolymers of PLA,such as lactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolide/ε-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically-3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates; such aspolyhydroxybutyrates)PHB); PHB/b-hydroxyvalerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone-poly-ε-capralactone,poly(ε-caprolactone-DL-lactide) copolymers; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinylalcohol (PVA); polypeptides; poly-b-malic acid (PMLA):poly-b-alkanbic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides); and mixtures thereof; and natural polymers, suchas sugars; starch, cellulose and cellulose derivatives, polysaccharides,collagen, chitosan, fibrin, hyalyronic acid, polypeptides and proteins.Mixtures of any of the above-mentioned polymers and their various formsmay also be used.

The biodegradable composite is preferably embodied in a polymer matrix,which may optionally comprise any of the above polymers. Optionally andpreferably, it may comprise a polymer selected from the group consistingof PLLA (poly-L-lactide), PDLLA (poly-DL-lactide), PLDLA, PGA(poly-glycolic acid), PLGA (poly-lactide-glycolic acid), PCL(Polycaprolactone), PLLA-PCL and a combination thereof. If PLLA is used,the matrix preferably comprises at least 30% PLLA, more preferably 50%,and most preferably at least 70% PLLA. If PDLA is used, the matrixpreferably comprises at least 5% PDLA, more preferably at least 10%,most preferably at least 20% PDLA.

Preferably, the inherent viscosity (IV) of the polymer matrix(independent of the reinforcement fiber) is in the range of 1.2 to 2.4dl/g, more preferably in the range of 1.5 to 2.1 dl/g, and mostpreferably in the range of 1.7 to 1.9 dl/g.

Inherent Viscosity (IV) is a viscometric method for measuring molecularsize. IV is based on the flow time of a polymer solution through anarrow capillary relative to the flow time of the pure solvent throughthe capillary.

Mineral composition may optionally include beta-tricalcium phosphate,calcium phosphate, calcium sulfate, hydroxyapatite, or a bioresorbableglass (also known as bioglass).

Bioresorbable glass fiber may optionally have oxide compositions in thefollowing mol. % ranges:

Na2O: 11.0-19.0 mol %.

CaO: 9.0-14.0 mol %.

MgO: 1.5-8.0 mol %.

B2O3: 0.5-3.0 mol %.

Al2O3: 0-0.8 mol %.

P2O3: 0.1-0.8 mol %.

SiO₂: 67-73 mol %.

And more preferably in the following mol. % ranges:

Na₂O: 12.0-13.0 mol %.

CaO: 9.0-10.0 mol %.

MgO: 7.0-8.0 mol %.

B2O3: 1.4-2.0 mol %.

P2O3: 0.5-0.8 mol %.

SiO2: 68-70 mol %.

Additional optional glass fiber compositions have been describedpreviously by Lehtonen T J et al. (Acta Biomaterialia 9 (2013)4868-4877), which is included here by reference in its entirety; suchglass fiber compositions may optionally be used in place of or inaddition to the above compositions.

Additional optional bioresorbable glass compositions are described inthe following patent applications, which are hereby incorporated byreference as if fully set forth herein, which are owned in common withthe instant application and which have inventor(s) in common:Biocompatible composite and its use (WO2010122098); and Resorbable andbiocompatible fibre glass compositions and their uses (WO2010122019).

In a more preferred embodiment of the present invention, the reinforcingfiller is bound to the bioabsorbable polymer such that the reinforcingeffect is maintained for an extended period. Such an approach has beendescribed in US 2012/0040002 A1 and EP 2243500B1, which discusses acomposite material comprising biocompatible glass, a biocompatiblematrix polymer and a coupling agent capable of forming covalent bonds.

Optionally, fibers may be aligned at an angle to the longitudinal axis(i.e. on a diagonal) such that and preferably, a majority ofreinforcement fibers are aligned at an angle that is less than 90°,alternatively less than 60°, or optionally less than 45° from thelongitudinal axis.

Medical Implant Composite Structure

Implant may be selected from a group that includes orthopedic pins,screws, plates, intramedullary rods, hip replacement, knee replacement,meshes, etc.

The average wall thickness in the implant is preferably in the range of0.2 to 10 mm, more preferably in the range of 0.4 to 5 mm, morepreferably in the range of 0.5 to 2 mm, and most preferably in the rangeof 0.5 to 1.5 mm.

The implant preferably comprises between 2-20 composite tape layers,more preferably between 2-10 layers, and most preferably between 2-6layers.

Optionally, implant may comprise reinforcing ribs, gussets, or struts.

Rib base thickness is preferably less than 100% of the adjoining wallthickness. More preferably, thickness is less than 85%, and mostpreferably less than 75%. Rib base thickness is preferably more than 20%of adjoining wall thickness, more preferably more than 30%, and mostpreferably more than 50% of adjoining wall thickness.

Preferably, rib height is at least 2.0 times the adjoining wallthickness, more preferably at least 3.0 times the wall thickness.

Draft angle of reinforcing ribs is preferably between 0.2-0.8°, morepreferably between 0.4-0.6°.

Preferably, distance between ribs is at least 2 times adjoining wallthickness. More preferably, at least 3 times adjoining wall thickness.

Preferably, reinforcing rib or other element increases bending stiffnessof implant by at least 20% without increasing compressive or tensilestiffness by more than 10%.

Optionally, ribs along one axis, for example the longitudinal axis ofthe implant, are taller than the ribs along the perpendicular axis, forexample the latitudinal axis of the implant, in order to facilitateeasier insertion of the implant.

Optionally, the implant may comprise one or more bosses to accommodatescrew insertion. Preferably, the boss is between 2-3 times the screwdiameter for self-tapping screw applications. Boss may additionallyinclude supportive gusses or ribs.

Optionally, one or more sides of implant may be textured.

Optionally, implant may contain continuous fibers aligned in a circulararrangement around holes, such as screw or pin holes, within theimplant.

Perforated Implant Part Walls

In some medical implants, it is desirable for there to be cellular ortissue ingrowth through the implant so as to strengthen theincorporation of the implant into the tissue and to increase complianceof the implant in physiological function. In order to further promotesuch ingrowth, it is beneficial to have gaps or holes in the walls ofthe herein described medical implant.

Preferably, if present, such perforations in implant walls comprise atleast 10% of the surface area of the implant, more preferably at least20%, at least 30%, at least 40%, or at least 50% of the surface area ofthe implant.

In one optional embodiment of the present invention, the implant is ascrew and the fenestrations of the threading contain perforation.

In one embodiment of the present invention, the implant containsperforations between composite tapes or between the reinforcement fiberswithin composite tapes making up the implant.

In a preferred embodiment, a majority of perforations are betweenreinforcement fibers and do not penetrate reinforcement fibers.

Cages Full of Bone Filler

In another embodiment of herein invention, the implant comprises anorthopedic implant and the implant forms a partial or full container andan osteoconductive or osteoinductive material is contained within theimplant container.

In a preferred embodiment, the implant container is additionallyperforated so as to allow improved bone ingrowth into theosteoconductive or osteoinductive material contained within the implantcage.

In an optional embodiment, the implant comprises an opening or doorthrough which bone filler can be introduced and/or bone ingrowth cantake place.

In an optional embodiment, the implant comprises two or more discreteparts or separate parts joined by a joint such that implant cage may befilled with bone filler material and subsequently assembled or closed totrap bone filler inside.

Framework of Continuous Fiber Reinforced Structure with Non-ReinforcedSurrounding Material

Whereas continuous fiber reinforced bioabsorbable composite structuresprovide the optimal mechanical strength and stiffness to a medicalimplant, it may also be beneficial in certain cases to have additionalfeatures or layers in the medical implant that cannot be made fromcontinuous fiber reinforced composite tapes. In such cases, themechanical strength of the continuous fiber reinforced bioabsorbablecomposite structures can be incorporated into the implant but additionalsections or layers of non-reinforced polymer may be added to improve orcustomize the implant. These sections or layers are preferably added tothe implant either by overmolding onto the structure or by 3-D printingonto the structure.

In one embodiment of the present invention, medical implant comprises astructural support comprised of a continuous fiber-reinforcedbioabsorbable composite material and additionally comprises a section orlayer comprised of non-reinforced polymer material.

Optionally the second layer functions as a bone interface layercomprised of a non-reinforced absorbable polymer material. Alsooptionally the structural support and non-reinforced polymer section areeach fabricated using a different production technique. Also optionallythe structural support is fabricated by machining, compression molding,or composite flow molding and the interface layer is fabricated byinjection molding or 3D printing; optionally the interface layer isfabricated on top of the prefabricated structural support.

Optionally the non-reinforced polymer section is a bone interface layerand dimensions of the interface layer are partially or entirelydetermined by the bone geometry of a specific patient or patientpopulation.

Optionally the bone geometry of patient or patient population isdetermined by measuring through imaging technique such as X-Ray, CT,MRI.

Optionally the elastic modulus and/or flexural strength of structuralsupport is at least 20% greater than that of the non-reinforced polymersection.

Optionally, continuous-fiber reinforced composite material in implant iscoated with a polymer resin wherein the polymer resin on fiber in thecomposite material has a higher or lower melting temp than the flowablematrix resin; or polymer resin on fiber has slower or faster degradationrate than flowable matrix resin; or polymer resin on fiber is morehydrophobic or more hydrophilic than flowable matrix resin

In an optional embodiment, an additional section or layer is comprisedof a reinforced polymer but where polymer is reinforced bynon-continuous fibers, preferably fibers less than 10 mm in length, andmore preferably less than 5 mm in length.

In an optional embodiment, an additional section or layer ofnon-reinforced or non-continuous fiber reinforced polymer additionalcomprises an additive.

Optionally, additive comprises an osteoconductive material orcombination of osteoconductive materials such as beta tricalciumphosphate, calcium phosphate, hydroxyapatite, decellularized bone.

Optionally, the additive comprises an anti-microbial agent or boneinducing agent.

Production Method

Continuous-fiber reinforced bioabsorbable implants may optionally beproduced using any method known in the art. Methods can includecompression molding, injection molding, extrusion, machining, or anycombination of these methods.

Preferably, moisture content of implant following production is lessthan 50%, more preferably less than 1%, even more preferably less than0.4%, 0.2%.

Low moisture content is important so as to avoid degradation of theimplant during storage.

Preferably, residual monomer content in implant following production isless than 3%, preferably less than 2%, and more preferably less than 1%.

Without wishing to be limited by a single hypothesis, where mineralcontent is high relative to biocomposite implants, it is particularlyimportant that the polymer component be predominantly comprised ofpolymer, with very low monomer component, since the monomer componentdoes not contribute to the mechanical function of the implant.

Implant Contact with Surrounding Tissue

In an optional embodiment of the present invention, less than 100% ofimplant surface area is in contact with surrounding tissue. This may beclinically desirable for several reasons:

1. Reduced friction with surrounding tissue upon insertion, easinginsertion

2. Reduced bone contact can reduce interference to bone surface bloodflow

In a preferred embodiment, implant contains surface protrusion elementsof at least 0.1 mm in height and less than 2 mm in height that come intocontact with tissue surrounding implant.

Preferably, total percentage of surface area of implant that comes intocontact with surrounding tissue is less than 80%, more preferably lessthan 60%, 50%, 40%, 30%.

Balloons

In an optional embodiment of herein invention, implant additionallycomprises a balloon. Balloon walls are preferably comprised of between1-3 layers of reinforced composite.

Fabrication of the Implant

Any of the above-described bioabsorbable polymers or reinforcedbioabsorbable polymers may be fabricated into any desired physical formfor use with the present invention. The polymeric substrate may befabricated for example, by compression molding, casting, injectionmolding, pultrusion, extrusion, filament winding, composite flow molding(CFM), machining, or any other fabrication technique known to thoseskilled in the art. The polymer may be made into any shape, such as, forexample, a plate, screw, nail, fiber, sheet, rod, staple, clip, needle,tube, foam, or any other configuration suitable for a medical device.

Load-Bearing Mechanical Strength

The herein invention particularly relates to bioabsorbable compositematerials that can be used in medical applications that require highstrength and a stiffness compared to the stiffness of bone. Thesemedical applications require the medical implant to bear all or part ofthe load applied by or to the body and can therefore be referred togenerally as “load-bearing” applications. These include fracturefixation, tendon reattachment, joint replacement, spinal fixation, andspinal cages.

The flexural strength preferred from the herein described load-bearingmedical implant is at least 100 MPa, preferably above 400 MPa, morepreferably above 600 MPa, and even more preferably above 800 MPa. TheElastic Modulus (or Young's Modulus) of the bioabsorbable composite foruse with herein invention is preferably at least 6 GPa, more preferablyabove 15 GPa, and even more preferably above 20 GPa but not exceeding100 GPa and preferably not exceeding 60 GPa.

Sustained Mechanical Strength

There is a need for the bioabsorbable load-bearing medical implants ofthe herein invention to maintain their mechanical properties (highstrength and stiffness) for an extended period to allow for sufficientbone healing. The strength and stiffness preferably remains above thestrength and stiffness of cortical bone, approximately 150-250 MPa and15-25 GPa respectively, for a period of at least 3 months, preferably atleast 6 months, and even more preferably for at least 9 months in vivo(i.e. in a physiological environment).

More preferably, the flexural strength remains above 400 MPa and evenmore preferably remains above 600 MPa.

In another embodiment of the present invention, the mechanical strengthdegradation rate of the medical implant approximates the materialdegradation rate of the implant, as measured by weight loss of thebiodegradable composite.

In a preferred embodiment, the implant retains greater than 50% of itsmechanical strength after 3 months of implantation while greater than50% of material degradation and hence weight loss occurs within 12months of implantation.

In a preferred embodiment, the implant retains greater than 70% of itsmechanical strength after 3 months of implantation while greater than70% of material degradation and hence weight loss occurs within 12months of implantation.

In a preferred embodiment, the implant retains greater than 50% of itsmechanical strength after 6 months of implantation while greater than50% of material degradation and hence weight loss occurs within 9 monthsof implantation.

In a preferred embodiment, the implant retains greater than 70% of itsmechanical strength after 6 months of implantation while greater than70% of material degradation and hence weight loss occurs within 9 monthsof implantation.

The mechanical strength degradation and material degradation (weightloss) rates of the medical implant can be measured after in vivoimplantation or after in vitro simulated implantation. In the case of invitro simulated implantation, the simulation may be performed in realtime or according to accelerated degradation standards.

“Biodegradable” as used herein is a generalized term that includesmaterials, for example polymers, which break down due to degradationwith dispersion in vivo. The decrease in mass of the biodegradablematerial within the body may be the result of a passive process, whichis catalyzed by the physicochemical conditions (e.g. humidity, pH value)within the host tissue. In a preferred embodiment of biodegradable, thedecrease in mass of the biodegradable material within the body may alsobe eliminated through natural pathways either because of simplefiltration of degradation by-products or after the material's metabolism(“Bioresorption” or “Bioabsorption”). In either case, the decrease inmass may result in a partial or total elimination of the initial foreignmaterial. In a preferred embodiment, said biodegradable compositecomprises a biodegradable polymer that undergoes a chain cleavage due tomacromolecular degradation in an aqueous environment.

A polymer is “absorbable” within the meaning of this invention if it iscapable of breaking down into small, non-toxic segments which can bemetabolized or eliminated from the body without harm. Generally,absorbable polymers swell, hydrolyze, and degrade upon exposure tobodily tissue, resulting in a significant weight loss. The hydrolysisreaction may be enzymatically catalyzed in some cases. Completebioabsorption, i.e. complete weight loss, may take some time, althoughpreferably complete bioabsorption occurs within 24 months, mostpreferably within 12 months.

The term “polymer degradation” means a decrease in the molecular weightof the respective polymer. With respect to the polymers, which arepreferably used within the scope of the present invention saiddegradation is induced by free water due to the cleavage of ester bonds.The degradation of the polymers as for example used in the biomaterialas described in the examples follows the principle of bulk erosion.Thereby a continuous decrease in molecular weight precedes a highlypronounced mass loss. Said mass loss is attributed to the solubility ofthe degradation products. Methods for determination of water inducedpolymer degradation are well known in the art such as titration of thedegradation products, viscometry, differential scanning calorimetry(DSC).

The term “Biocomposite” as used herein is a composite material formed bya matrix and a reinforcement of fibers wherein both the matrix andfibers are biocompatible and optionally bioabsorbable. In most cases,the matrix is a polymer resin, and more specifically a syntheticbioabsorbable polymer. The fibers are optionally and preferably of adifferent class of material (i.e. not a synthetic bioabsorbablepolymer), and may optionally comprise mineral, ceramic, cellulosic, orother type of material.

Clinical Applications

The medical implants discussed herein are generally used for bonefracture reduction and fixation to restore anatomical relationships.Such fixation optionally and preferably includes one or more, and morepreferably all, of stable fixation, preservation of blood supply to thebone and surrounding soft tissue, and early, active mobilization of thepart and patient.

There are several exemplary, illustrative, non-limiting types of bonefixation implants for which the materials and concepts describedaccording to at least some embodiments of the present invention may berelevant, as follows:

Bone Plate

A bone plate is typically used to maintain different parts of afractured or otherwise severed bone substantially stationary relative toeach other during and/or after the healing process in which the bonemends together. Bones of the limbs include a shaft with a head at eitherend thereof. The shaft of the bone is generally elongated and ofrelatively cylindrical shape.

It is known to provide a bone plate which attaches to the shaft or headand shaft of a fractured bone to maintain two or more pieces of the bonein a substantially stationary position relative to the one another. Sucha bone plate generally comprises a shape having opposing substantiallyparallel sides and a plurality of bores extending between the opposingsides, wherein the bores are suitable for the receipt of pins or screwsto attach the plate to the bone fragments.

For proper function of the bone plate in maintaining different parts ofa fractured bone stationary relative to each other, the plate must be ofsufficient mechanical strength and stiffness to maintain the position ofthe bone fragments or pieces. However, it must achieve these mechanicalproperties within a low profile thickness profile to ensure that therewill be sufficient space for the bone plate to fit between bone and thesurrounding soft tissue. The thickness of the bone plate is generally inthe range of 2.0 mm to 8.0 mm and more commonly in the range of 2.0 mmto 4.0 mm. The widths of the plates are variable but

Screws

Screws are used for internal bone fixation and there are differentdesigns based on the type of fracture and how the screw will be used.Screws come in different sizes for use with bones of different sizes.Screws can be used alone to hold a fracture, as well as with plates,rods, or nails. After the bone heals, screws may be either left in placeor removed.

Screws are threaded, though threading can be either complete or partial.Screws can include compression screws, locking screws, and/or cannulatedscrews. External screw diameter can be as small as 0.5 or 1.0 mm but isgenerally less than 3.0 mm for smaller bone fixation. Larger bonecortical screws can be up to 5.0 mm and cancellous screws can even reach7-8 mm. Some screws are self-tapping and others require drilling priorto insertion of the screw. For cannulated screws, a hollow section inthe middle is generally larger than 1 mm diameter in order toaccommodate guide wires.

Wires/Pins

Wires are often used to pin bones back together. They are often used tohold together pieces of bone that are too small to be fixed with screws.They can be used in conjunction with other forms of internal fixation,but they can be used alone to treat fractures of small bones, such asthose found in the hand or foot. Wires or pins may have sharp points oneither one side or both sides for insertion or drilling into the bone.

“K-wire” is a particular type of wire generally made from stainlesssteel, titanium, or nitinol and of dimensions in the range of 0.5-2.0 mmdiameter and 2-25 cm length. “Steinman pins” are general in the range of2.0-5.0 mm diameter and 2-25 cm length. Nonetheless, the terms pin andwire for bone fixation are used herein interchangeably.

Anchors

Anchors and particularly suture anchors are fixation devices for fixingtendons and ligaments to bone. They are comprised of an anchormechanism, which is inserted into the bone, and one or more eyelets,holes or loops in the anchor through which the suture passes. This linksthe anchor to the suture. The anchor which is inserted into the bone maybe a screw mechanism or an interference mechanism. Anchors are generallyin the range of 1.0-6.5 mm diameter

Cable, Ties, Wire Ties

Cables, ties, or wire ties can be used to perform fixation by cerclage,or binding, bones together. Such implants may optionally hold togetherbone that cannot be fixated using penetration screws or wires/pin,either due to bone damage or presence of implant shaft within bone.Generally, diameter of such cable or tie implants is optionally in therange of 1.0 mm-2.0 mm and preferably in the range of 1.25-1.75 mm. Wiretie width may optionally be in the range of 1-10 mm.

Nails or Rods

In some fractures of the long bones, medical best practice to hold thebone pieces together is through insertion of a rod or nail through thehollow center of the bone that normally contains some marrow. Screws ateach end of the rod are used to keep the fracture from shortening orrotating, and also hold the rod in place until the fracture has healed.Rods and screws may be left in the bone after healing is complete. Nailsor rods for bone fixation are generally 20-50 cm in length and 5-20 mmin diameter (preferably 9-16 mm). A hollow section in the middle of nailor rod is generally larger than 1 mm diameter in order to accommodateguide wires.

Any of the above-described bone fixation implants may optionally be usedto fixate various fracture types including but not limited to comminutedfractures, segmental fractures, non-union fractures, fractures with boneloss, proximal and distal fractures, diaphyseal fractures, osteotomysites, etc.

Example #1—Large Diameter Pins

Below example describes production of large diameter orthopedic pinswith reinforced biocomposite materials. This example demonstrates howdifferent medical implant pins comprised of reinforced biocompositematerials can have different performance properties with regard toflexural modulus and strength, both at time zero (following production)and following simulated degradation, relating to the compositionalstructure, geometry, and composition of each type of pin.

Materials & Methods

Three types of pin implants, each of outer diameter 6 mm and 5 cm lengthwere produced using reinforced composite material. Material compositewas comprised of PLDLA 70/30 polymer reinforced with 50% w/w, 70%, or85% w/w continuous mineral fibers. Mineral fibers composition wasapproximately Na₂O 14%, MgO 5.4%, CaO 9%, B₂O₃ 2.3%, P₂O₅ 1.5%, and SiO₂67.8% w/w. Testing samples were manufactured by compression molding ofmultiple layers of composite material into a tubular mold, either withor without a 3 mm pin insert in the center. Each layer was comprised ofthe PLDLA polymer with embedded uni-directionally aligned continuousfibers. Orientation of layers relative to longitudinal axis of implantwere 0° (parallel to implant longitudinal axis), 45°, 0°, −45°, 0°, in arepetitive manner according to number of layers in the implant. Eachlayer was approximately 0.18 mm thick. Three (3) pin samples wereproduced for each pin group.

Implant samples were tested in a tensile testing system (220Q1125-95,TestResources, MN, USA) for flexural strength, flexural modulus andmaximum flexural load according to modified standard test method, ASTMD790 (Standard Test Methods for Flexural Properties of Unreinforced andReinforced Plastics and Electrical Insulating Materials,http://www.astm.org/Standards/D790.htm, ASTM International, PA, USA).Testing was conducted initially and following simulated in vitrodegradation according to modified ASTM F1635 (Standard Test Method forin vitro Degradation Testing of Hydrolytically Degradable Polymer Resinsand Fabricated Forms for Surgical Implants,http://www.astm.org/Standards/F1635.htm ASTM International, PA, USA),wherein samples were incubated in simulated body fluid (SBF), 142 Na⁺, 5K⁺, 1.5 Mg²⁺, 2.5 Ca²⁺, 147.8 Cl⁻, 4.2 HCO₃ ⁻, 1 HPO₄ ³⁻, 0.5 SO₄ ²⁻mol/m³, for 5 days at a temperature of 50° C., while shaking at 30 rpm.Mechanical testing was performed using a 5 KN load cell and anappropriate fixture for three point bending testing. Sample span was 40mm at the beginning of the test and cross head speed was set at 2mm/min. Dimensions, weight and density of samples were recorded.

Scanning electron microscope (SEM) (FEI Quanta FEG 250, Holland) imageswere captured for cross-sections of implant samples at severalmagnifications, with and without Au sputtering, and using either SE orBSE detectors. ImageJ™ (NIH Image Processing Software,http://www.imagej.nih.gov/ij/, National Institute of Health, Maryland,USA) was used to count or measure the following parameters:

-   -   1. Distance between fibers    -   2. Distance between layers    -   3. Number of fibers per layer    -   4. Fiber diameter    -   5. Tangential angle to curvature

MATLAB (http://www.mathworks.com/products/matlab/, Mathworks, MA, USA)was used to count or measure the following parameters:

-   -   1. Volume distribution of fibers within cross section of implant

Results

Table 1a shows the mechanical performance results of implant pins madefrom three different types of reinforced composites as described above.The structural properties of these implants are described by theproduction methods discussed above and their internal compositions areseen in the associated images. Quantification of several parametersrelated to the internal composition structure of the implants can beseen in table 1b.

TABLE 1a Mean values and standard deviations of the mechanicalproperties and bulk properties of the implants (n = 3). Flexural MaxStrength Load Density Volume Pin Type E [MPa] [MPa] [N] [gr/ml] [mm³]Full pin. OD 8697.0 ± 237.8 243.7 ± 14.5 549.6 ± 57.3 1.60 1472.7 6 mm.50% w/w fiber. T = 0 Full pin. OD 6423.5 ± 243.6 118.6 ± 16.6 267.9 ±41.3 1.64 1480.5 6 mm. 50% w/w fiber. T = 5 d Full pin. OD 14207.5 ±811.7  224.6 ± 51.6  455.1 ± 130.5 1.83 1365.9 6 mm. 70% w/w fiber. T =0 Full pin. OD 6745.0 ± 677.6  85.1 ± 15.2 209.7 ± 48.6 1.78 1567.7 6mm. 70% w/w fiber. T = 5 d Hollow pin. OD  7244.6 ± 1736.9 148.5 ± 5.4 294.0 ± 5.1  1.58 1067.4 6 mm. ID 3 mm. 50% w/w fiber. T = 0 Hollow pin.OD  4281.6 ± 1608.2  81.2 ± 12.5 169.6 ± 27.4 1.63 1113.1 6 mm. ID 3 mm.50% w/w fiber. T = 5 d

Full pin samples produced with OD 6 mm, 85% w/w fiber severely lacked incohesive strength, likely due to insufficient amount of polymer bindingbetween fiber layers. These samples failed during loading onto thetensile testing system and therefore mechanical property results werenot recorded. Images of these pins can be seen in FIGS. 27 and 28, whichshow high amount of fibers and absence of polymer.

As can be seen in Table 1A, incubation for 5 days in SBF at 50° C.,which accelerates degradation rate, resulted in a decrease in modulus of26%, 53% and 41% in the full 50% w/w, full 70% w/w and hollow 6 mm pinsrespectively. Incubation for 5 days in SBF at 50° C., which acceleratesdegradation rate, resulted in a decrease in flexural strength of 51%,62% and 45% in the full 50% w/w, full 70% w/w and hollow 6 mm pinsrespectively. Incubation for 5 days in SBF at 50° C., which acceleratesdegradation rate, resulted in a decrease in maximum flexural load of51%, 53% and 42% in the full 50% w/w, full 70% w/w and hollow 6 mm pinsrespectively.

TABLE 1b Measured structural parameters relating the reinforcing fibersand biocomposite layers within two types of biocomposite pins. FiberDistance diameter Distance Fibers in between range between layer Layerlayers (μm) fibers (μm) thickness thickness (μm) (μm) Full 9.38-12.831.39-8.7 7-9 92.6-185.0 28.77-50.05 pin. OD (FIG. (FIG. 2) (FIG. 3)(FIG. 3, 4) (FIG. 6 mm. 50% 1) 5) w/w fiber Full 4.63-31.45 9-13 161.52(FIG. pin. OD (FIG. (FIG. 7) 6 mm. 70% 6) 7) w/w fiber

Without wishing to be limited by a single hypothesis, it is believedthat reinforcing fiber content, diameter, distribution, and arrangementinto layers seen in this example (Example 1) were the cause or at leasta significantly contributing factor.

Specifically with regard to reinforcing fiber, increasing reinforcingfiber content may contribute positively to mechanical properties of amedical implant, as seen by the stronger and stiffer samples producedwith 70% fiber as compared with those produced with 50% fiber. However,the 70% fiber implants seemed to lose mechanical properties at a fasterrate. Thus, there are potential benefits to each of these amount offibers. Above a certain point, overly high fiber content can result infailure of the implant, as observed with the 85% fiber pins.

Example #2—Small Diameter Pins

Below example describes production of small diameter orthopedic pinswith reinforced biocomposite materials. This example demonstrates howdifferent medical implant pins comprised of reinforced biocompositematerials can have different performance properties with regard toflexural modulus and strength, both at time zero (following production)and following simulated degradation (for example upon insertion to thebody), relating to the compositional structure, geometry, andcomposition of each type of pin.

Materials & Methods

Three types of pin implants, each of outer diameter 2 mm and 5 cm lengthwere produced using reinforced composite material. Material compositewas comprised of PLDLA 70/30 polymer reinforced with 50% w/w or 70% w/wcontinuous mineral fibers. Mineral fiber composition was approximatelyNa₂O 14%, MgO 5.4%, CaO 9%, B₂O₃ 2.3%, P₂O₅ 1.5%, and SiO₂ 67.8% w/w.Testing samples were manufactured by compression molding of multiplelayers of composite material into a tubular mold, either with or withouta 1 mm pin insert in the center. Each layer was comprised of the PLDLApolymer with embedded uni-directionally aligned continuous fibers.Orientation of layers relative to longitudinal axis of implant were 0°(parallel to implant longitudinal axis), 45°, 0°, −45°, 0°, in arepetitive manner according to number of layers in the implant. Eachlayer was approximately 0.18 mm thick. Three (3) pin samples wereproduced for each pin group.

Implant samples were tested in a tensile testing system (220Q1125-95,TestResources, MN, USA) for flexural strength, flexural modulus andmaximum flexural load according to modified standard test method, ASTMD790 (Standard Test Methods for Flexural Properties of Unreinforced andReinforced Plastics and Electrical Insulating Materials,http://www.astm.org/Standards/D790.htm, ASTM International, PA, USA).Testing was conducted initially and following simulated in vitrodegradation according to modified ASTM F1635, (Standard Test Method forin vitro Degradation Testing of Hydrolytically Degradable Polymer Resinsand Fabricated Forms for Surgical Implants,http://www.astm.org/Standards/F1635.htm ASTM International, PA, USA)wherein samples were incubated in simulated body fluid (SBF), 142 Na⁺, 5K⁺, 1.5 Mg²⁺, 2.5 Ca²⁺, 147.8 Cl⁻, 4.2 HCO₃ ⁻, 1 HPO₄ ³⁻, 0.5 SO₄ ²⁻mol/m³, for 5 days at a temperature of 50° C., while shaking at 30 rpm.Mechanical testing was performed using a 500 N load cell and anappropriate fixture for three point bending testing. Sample span was 40mm at the beginning of the test and cross head speed was set at 2mm/min. Dimensions, weight and density of samples were recorded.

Scanning electron microscope (SEM) (FEI Quanta FEG 250, Holland) imageswere captured for cross-sections of implant samples at severalmagnifications, with and without Au sputtering, and using either SE orBSE detectors. ImageJ™ (NIH Image Processing Software,http://www.imagej.nih.gov/ij/, National Institute of Health, Maryland,USA) was used to count or measure the following parameters:

-   -   1. Distance between fibers    -   2. Distance between layers    -   3. Number of fibers per layer    -   4. Fiber diameter    -   5. Tangential angle to curvature

MATLAB (http://www.mathwork.com/products/matlab/, Mathworks, MA, USA)was used to count or measure the following parameters:

-   -   1. Volume distribution of fibers within cross section of        implant: The percentage of fiber to polymer was calculated by        summing the entire fiber area in the image divided by the area        of the entire implant cross section in the image.        Percentage of Fiber to Polymer=Sum of Fiber AreaArea of Entire        Cross Section*100

Results

Table 2a shows the mechanical performance results of three differenttypes of reinforced composites implant pins produced as described above.The structural properties of these implants are described by theproduction methods discussed above and their internal compositions areseen in the associated images. Quantification of several parametersrelated to the internal composition structure of the implants can beseen in tables 2b, c and d.

TABLE 2a Mean values and standard deviations of the mechanicalproperties and bulk properties of the implants (n = 3). Flexural EStrength Max Load Density Volume Pin Type [MPa] [MPa] [N] [gr/ml] [mm³]Full pin. OD 273.6 ± 48.3 11761.0 ± 1028.8  25.7 ± 3.79 1.43 180.7 2 mm.50% w/w fiber. T = 0 Full pin. OD 127.2 ± 23.4 11954.9 ± 2885.5 12.45 ±2.4  1.37 185.88 2 mm. 50% w/w fiber. T = 5 d Full pin. OD 290.6 ± 2.7 14062.2 ± 2158.3 30.16 ± 1.6  1.55 192.43 2 mm. 70% w/w fiber. T = 0Full pin. OD  78.9 ± 14.4 9931.5 ± 358.8 8.65 ± 1.2 1.57 201.7 2 mm. 70%w/w fiber. T = 5 d Hollow pin. OD 136.6 ± 11.7 10231.3 ± 1609.2 14.1 ±1.1 1.37 157.6 2 mm. ID 1 mm. 50% w/w fiber. T = 0 Hollow pin. OD 100.1± 16.5  6913.7 ± 2420.1 10.35 ± 2.11 1.56 158.1 2 mm. ID 1 mm. 50% w/wfiber. T = 5 d

Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in flexural strength of 54%, 27% and 73% inthe full 50% w/w, full 70% w/w and hollow 2 mm pins respectively.Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in maximum flexural load of 52%, 27% and71% in the full 50% w/w, full 70% w/w and hollow 2 mm pins respectively.Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in flexural modulus of 32% and 29% in thefull 70% w/w and hollow 2 mm 50% w/w pins respectively.

TABLE 2b Measured structural parameters relating the reinforcing fibersand biocomposite layers within a biocomposite pin Fiber Distancediameter Distance Fibers in Layer between range between layer thicknesslayers (μm) fibers (μm) thickness (μm) (μm) Full 10.18-13.5 2.80-16.024-6 91.09 (FIG. 14.35-41.59 pin. OD (FIG. (FIG. 9) (FIG. 10) 10) (FIG. 2mm. 50% 8) 12) w/w fiber Hollow 11-15 2.04-10.11 11.96-33.6 pin. OD(FIG. 13) (FIG. (FIG. 2 mm, ID 14) 16) 1 mm. 50% w/w fiber

TABLE 2c Measured volume percentage of fiber as measured fromcross-section of biocomposite full pin implant of OD 2 mm, 50% w/w fiber(see FIG. 11) Area of Entire Remaining Percentage of Cross Section Sumof Fiber Area Area Fiber to Polymer 22579 μm 11043 μm 1.1536e+04 μm48.90%

TABLE 2d Measured volume percentage of fiber as measured fromcross-section of biocomposite full plate implant of OD 2 mm, ID 1 mm,50% w/w fiber (see FIG. 15) Area of Entire Remaining Percentage of CrossSection Sum of Fiber Area Area Fiber to Polymer 14094 μm 9645.14 μm4448.86 μm 68.43%

Without wishing to be limited by a single hypothesis, it is believedthat reinforcing fiber content, diameter, distribution, and arrangementinto layers seen in this example (Example 2) were the cause or at leasta significantly contributing factor.

This example also suggests a potential structural difference betweendifferent implant part geometries (between a full pin and cannulatedpin), where it is optionally possible for reinforcing fiber layers inthe biocomposite implant to arrange and align themselves in differentialmanners depending on the shape of the implant and the forces that theimplant is exposed to during its production.

Example #3—Plates

Below example describes production of thin orthopedic plates withreinforced biocomposite materials. This example demonstrates howdifferent medical implant plates comprised of reinforced biocompositematerials can have different performance properties with regard toflexural modulus and strength, both at time zero (following production)and following simulated degradation, relating to the compositionalstructure, geometry, and composition of each type of plate.

Materials & Methods

Four types of plate implants, each with a thickness of 2 mm, width of12.8 mm and 6 cm length were produced using reinforced compositematerial. Material composite was comprised of PLDLA 70/30 polymerreinforced with 50% w/w or 70% w/w continuous mineral fibers. Mineralfibers composition was approximately Na₂O 14%, MgO 5.4%, CaO 9%, B₂O₃2.3%, P₂O₅ 1.5%, and SiO₂ 67.8% w/w. Testing samples were manufacturedby compression molding of multiple layers of composite material into arectangle mold. Each layer was comprised of the PLDLA polymer withembedded uni-directionally aligned continuous fibers. Orientation oflayers relative to longitudinal axis of implant were 0° (parallel toimplant longitudinal axis), 45°, 0°, −45°, 0°, in a repetitive manneraccording to number of layers in the implant. Each layer wasapproximately 0.18 mm thick. For the amorphous plates, continuous fiberswere cut to small pieces, mixed and molded. Three (3) plate samples wereproduced for each plate group.

Implant samples were tested in a tensile testing system (220Q1125-95,TestResources, MN, USA) for flexural strength, flexural modulus andmaximum flexural load according to modified standard test method, ASTMD790 (Standard Test Methods for Flexural Properties of Unreinforced andReinforced Plastics and Electrical Insulating Materials,http://www.astm.org/Standards/D790.htm, ASTM International, PA, USA).Testing was conducted initially and following simulated in vitrodegradation according to modified ASTM F1635, (Standard Test Method forin vitro Degradation Testing of Hydrolytically Degradable Polymer Resinsand Fabricated Forms for Surgical Implants,http://www.astm.org/Standards/F1635.htm ASTM International, PA, USA)wherein samples were incubated in simulated body fluid (SBF), 142 Na⁺, 5K⁺, 1.5 Mg²⁺, 2.5 Ca²⁺, 147.8 Cl⁻, 4.2 HCO₃ ⁻, 1 HPO₄ ³⁻, 0.5 SO₄ ²⁻mol/m³, for 5 days at a temperature of 50° C., while shaking at 30 rpm.Mechanical testing was performed using a 5 KN load cell and anappropriate fixture for three point bending testing. Sample span was 40mm at the beginning of the test and cross head speed was set at 2mm/min. Dimensions, weight and density of samples were recorded.

Scanning electron microscope (SEM) (FEI Quanta FEG 250, Holland) imageswere captured for cross-sections of implant samples at severalmagnifications, with and without Au sputtering, and using either SE orBSE detectors. ImageJ™ (NIH Image Processing Software,http://www.imagej.nih.gov/ij/, National Institute of Health, Maryland,USA) was used to count or measure the following parameters:

-   -   1. Distance between fibers    -   2. Distance between layers    -   3. Number of fibers per layer    -   4. Fiber diameter    -   5. Tangential angle to curvature

MATLAB (http://www.mathworks.com/products/matlab/, Mathworks, MA, USA)was used to count or measure the following parameters:

-   -   1. Volume distribution of fibers within cross section of implant

Results

Table 3a shows the mechanical performance results of three differenttypes of reinforced composites implant pins produced as described above.The structural properties of these implants are described by theproduction methods discussed above and their internal compositions areseen in the associated images. Quantification of several parametersrelated to the internal composition structure of the implants can beseen in table 3b.

TABLE 3a Mean values and standard deviations of the mechanicalproperties and bulk properties of the implants (n = 3). Flexural Max EStrength Load Density Volume Plate Type [MPa] [MPa] [N] [gr/ml] [mm³]Plate. 50% w/w 306.9 ± 13.9 15362.1 ± 502.4 285.27 ± 7.7   1.65 1624.8fiber. T = 0 Plate. 50% w/w 127.0 ± 39.1 11063.3 ± 688.8 143.5 ± 41.7 1.6 1786 fiber. T = 5 d Plate. 70% w/w  358.5 ± 142.9  23088.4 ± 2012.5307.56 ± 121   1.89 1552.0 fiber. T = 0 Plate. 70% w/w fiber.  83.2 ±34.3  10806.9 ± 1463.3 115.76 ± 115.8  1.7 1947.7 T = 5 d Plate.Amorphous 108.1 ± 16.5  8299.7 ± 1276.9 97.4 ± 17.0 1.66 1595.1 50% w/wfiber. T = 0

Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in flexural modulus of 27% and 53% in thefull 50% w/w and full 70% w/w plates respectively. Incubation for 5 daysin SBF at 50° C., which accelerates degradation rate, resulted in adecrease in flexural strength of 58% and 76% in the full 50% w/w andfull 70% w/w plates respectively.

Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in maximum flexural load of 50% and 62% inthe full 50% w/w and full 70% w/w plates respectively.

For this geometry and production method it seems that the increase infiber content from 50% to 70 w/w, increases the initial mechanicalstrength but accelerates the degradation process.

Having short non oriented fibers as exist in the amorphous plate versuscontinuously oriented fibers resulted in a decrease of 46%, 65% and 66%in the modulus, flexural strength and maximum load for a similar densityand production conditions.

TABLE 3b Measured structural parameters relating the reinforcing fibersand biocomposite layers within a biocomposite plate Fiber Distancediameter Distance Fibers in Layer between range between layer thicknesslayers (μm) fibers (μm) thickness (μm) (μm) Plate. 11.48-13.98 2.32-9.8850% (FIG. (FIG. w/w 17) 18) fiber Plate. 3.04-20 6-10 70.03-110.863.77-15.99 70% (FIG. (FIG. (FIG. 20) (FIG. 21) w/w 19) 20) fiber

Example #4—Degradation Differences

Below example describes the degradation of orthopedic implants producedwith reinforced biocomposite materials. This example demonstrates howdifferent medical implants comprised of reinforced biocompositematerials can differ in performance properties with regards to materialloss and swelling ratio following simulated degradation. An absorbableorthopedic implant, used for bone fixation, as intended for thefollowing, ideally needs to retain its strength for the period neededfor the bone to heal, and then gradually degrade and lose its strengthas it is replaced by bone. Material weight loss is an indication for therate of degradation. Swelling ratio is an indication for conformationalchanges, hydrophilicity as well as an indication for porosity. Controlof both parameters are important for implant design.

Materials & Methods

Pin and plate implants were produced using reinforced composite materialas described in example 1-3. Material composite was comprised of PLDLA70/30 polymer reinforced with 50% w/w or 70% w/w continuous mineralfibers. Mineral fibers composition was approximately Na₂O 14%, MgO 5.4%,CaO 9%, B₂O₃ 2.3%, P₂O₅ 1.5%, and SiO₂ 67.8% w/w. Testing samples weremanufactured by compression molding of multiple layers of compositematerial into an appropriate mold. Each layer was comprised of the PLDLApolymer with embedded uni-directionally aligned continuous fibers.Orientation of layers relative to longitudinal axis of implant were 0°(parallel to implant longitudinal axis), 45°, 0°, −45°, 0°, in arepetitive manner according to number of layers in the implant. Eachlayer was approximately 0.18 mm thick. Three (3) implant samples wereproduced for each group.

Implant samples were weighed initially and following simulated in vitrodegradation according to a modified ASTM F1635, wherein samples wereincubated in simulated body fluid (SBF), 142 Na⁺, 5 K⁺, 1.5 Mg²⁺, 2.5Ca²⁺, 147.8 Cl⁻, 4.2 HCO₃ ⁻, 1 HPO₄ ³⁻, 0.5 SO₄ ²⁻ mol/m³, for 5 days ata temperature of 50° C., while shaking at 30 rpm. Samples were thendried in a vacuum desiccator overnight and weighed again. Materialpercentage loss was calculated as (initial weight−dried weight)/initialweight*100. Swelling ratio was calculated as (weight at the end of theincubation−dried weight)/dried weight*100.

Results

Table 4 shows the weight measurement results of different types ofreinforced composite implants produced as described above.

TABLE 4 Mean values and standard deviations of implant weightmeasurements and calculated material loss and swelling ratio (n = 3).Measurements are of the weight at the beginning of the experiment (T0),after degradation of 5 days in SBF at 50° C., 30 rpm (5 days) and afterdehydration in the desiccator overnight (dried). 5 Days Dried MaterialSwelling T0 [gr] [gr] [gr] loss (%) ratio (%) Full pin. OD 2.33 ± 0.092.43 ± 0.09 2.35 ± 0.09 0.245 4.42 6 mm. 50% w/w Full pin. OD 2.68 ±0.09 2.79 ± 0.01 2.69 ± 0.01 0.262 4.35 6 mm. 70% w/w Hollow pin. OD1.69 ± 0.01 1.81 ± 0.01 1.69 ± 0.01 0.262 7.57 6 mm. ID 3 mm. 50% w/wFull pin. OD 0.257 ± 0.01  0.273 ± 0.01  0.254 ± 0.01  1.24 7.456 2 mm.50% w/w Full pin. OD 0.281 ± 0.02  0.317 ± 0.03  0.274 ± 0.02  2.615.626 2 mm. 70% w/w Hollow pin. OD 0.226 ± 0.03  0.246 ± 0.02  0.221 ±0.02  2.085 11.347 2 mm. ID 1 mm. 50% w/w Plate. 50% w/w 2.755 ± 0.01 2.870 ± 0.01  2.75 ± 0.01 0.143 4.353 fiber Plate. 70% w/w 3.158 ± 0.3 3.346 ± 0.3  3.149 ± 0.25  0.312 6.237 fiber

Mineral fiber concentration increase from 50% to 70%, in the 2 mm pinsand plates, increased the material loss and the swelling ratio over timeby ˜110% and more than 40% respectively. Relative degradation, asmeasured by relative material loss, seemed to be faster in cannulatedimplants vs non cannulated designs.

In the 6 mm pins, mineral fiber concentration increase from 50% to 70%also caused an increase in degradation as measured by material loss %.In the 6 mm cannulated pins, the relative degradation increase couldalso be noted by the increase in swelling ratio of 74% vs the full pins.

Example 5—Mineral Content

In the current example, biocomposite implant samples are demonstratedthat comprise 50, 60 and 70% mineral content. These samples have bothhigh mineral content and high mechanical properties.

This example further demonstrates the difference between medical implantmechanical properties at time=0 and following 5 days of simulatedbioabsorption. In many cases, the mechanical properties (includingflexural modulus, flexural strength, and maximum load) of the implantswith 50% mineral content were lower than the mechanical properties ofthe corresponding implants with higher mineral content at time=0.However, after 5 days of simulated bioabsorption, the mechanicalproperties of implants with higher mineral content (60% or 70%) droppedfurther than the 50% mineral content implants. As such, the long termperformance of the 50% mineral content implant would be improved ascompared with the higher mineral content implants. However, an initiallystronger implant can be achieved with higher mineral contents.

Methods & Materials

Three types of biocomposite implants were produced: pin of outerdiameter 2 mm, pin of outer diameter 6 mm, and rectangular plates(60×27×1.5 mm). Each sample was of 7 cm length. Material composite wascomprised of PLDLA 70/30 polymer reinforced with 50% w/w, 60% w/w or 70%w/w continuous mineral fibers. Mineral fibers composition wasapproximately Na₂O 14%, MgO 5.4%, CaO 9%, B₂O₃ 2.3%, P₂O₅ 1.5%, and SiO₂67.8% w/w. Testing samples were manufactured by compression molding ofmultiple layers of composite material into a tubular mold or rectangularmold. Each layer was comprised of the PLDLA polymer with embeddeduni-directionally aligned continuous fibers. Orientation of layersrelative to longitudinal axis of implant were 0° (parallel to implantlongitudinal axis), 45°, 0°, −45°, 0°, in a repetitive manner accordingto a number of layers in the implant. Each layer was approximately 0.18mm thick. Three (3) samples were produced for each group. Mechanicalproperties were tested in a three point bending test.

Results

2 mm pins Flexural E [Mpa] Strength [Mpa] Max Load [N] T0 5 days T0 5days T0 5 days 50% 11761.0055 11954.8476 273.5469 127.1556 25.664712.453 60% 17772.9284 10858.1928 339.9570 95.0317 30.5300 11.1593 70%14062.1921 9931.4495 290.5704 78.8613 30.1587 8.6517

Plates Flexural E [Mpa] Strength [Mpa] Max Load [N] T0 5 days T0 5 daysT0 5 days 50% 15362.1439 11063.2504 306.8561 127.0402 285.2700 143.500070% 23088.3630 10806.9162 358.4756 83.1500 307.5633 115.7633

6 mm pins Flexural E [Mpa] Strength [Mpa] Max Load [N] T0 5 days T0 5days T0 5 days 50% 8696.9920 6423.4802 243.6777 118.6093 549.6000267.8900 70% 14207.5159 6744.9709 224.6186 85.0544 455.0700 209.7467

Example 6—Additional Drawings Showing Various Embodiments

FIG. 30 shows a continuous fiber-reinforced tape of the type that can beused to form a layer in a medical implant comprised of continuousfiber-reinforced layers. The top view (3000) shows a single strip ofcomposite tape comprising reinforcement fibers aligned in a singledirection within a bioabsorbable polymer matrix. The interspersedreinforcement fibers (3006) within the bioabsorbable polymer matrix(3008) can be seen more clearly in the close-up top view (3002) of thecontinuous-fiber reinforced composite tape. The reinforcement fibers canbe present as separate fibers or in bundles of several reinforcementfibers per bundle. The cross-sectional view of the continuous fiberreinforced tape (3004) shows the bundles of aligned reinforcement fibers(3010) embedded within the bioabsorbable polymer matrix (3012). Fiberspreferably do not breach the surface of the bioabsorbable polymermatrix.

FIG. 31 shows a cut-away, three-dimensional view of a continuousfiber-reinforced tape (200). The cut-away view shows the alignedreinforcement fibers (202) embedded within the bioabsorbable polymermatrix (204).

FIG. 32a shows a top-view of a reinforced bioabsorbable composite sheet(300) comprised of three layers of uni-directional fibers at differentangles. Each layer can optionally be comprised of continuous fiberreinforced tapes of the type depicted in

FIG. 30. The expanded view (302) shows layers of uni-directional fibersat different angles within an implant. One layer (304) aligned in thelongitudinal axis, one layer (306) aligned at an angle to the right ofthe longitudinal axis, and one layer (308) aligned at an angle to theleft of the longitudinal axis.

FIG. 32b shows a cut-away view of a reinforced bioabsorbable compositestructure (310) comprised of three layers of uni-directional fibers atdifferent angles. One layer (312) aligned in the longitudinal axis, onelayer (314) aligned at an angle to the right of the longitudinal axis,and one layer (316) aligned at an angle to the left of the longitudinalaxis. Each layer is comprised of reinforced continuous fibers (318)embedded within bioabsorbable polymer matrix (320).

FIG. 33 shows the wall of a continuous-fiber reinforced compositemedical implant. The implant wall is comprised of two layers ofuni-directional continuous-fiber reinforced composite tape layers (402 &404) aligned at a perpendicular angle to each other. The medical implantwall additional comprises perforations (406) to allow for tissuepenetration into or through the implant.

FIG. 34 shows a bone filler cage that consists of continuous-fiberreinforced composite medical implant walls (500) that additionallycontains perforations (502) to allow tissue and cellular ingrowth intothe bone filler material (504) contained within the bone filler cage.The bone filler cage optionally includes a separate door to close thecage (506).

FIG. 35 shows a bioabsorbable cannulated screw (600) that is a medicalimplant comprised of two parts: a continuous-fiber reinforcedbioabsorbable composite cylindrical core (602) and bioabsorbable polymerthreading (604) that was subsequently molded or 3D printed on top of thecontinuous-fiber core. This is an example of a bioabsorbable medicalimplant where a significant amount or majority of the mechanicalstrength is provided by a continuous-fiber reinforced part that servesas a mechanical support or structure but where additional implantfeatures are comprised of materials that are not continuous fiberreinforced and yet can be molded or printed directly onto the fiberreinforced composite material.

Example 7—Mineral Content

In the current example, biocomposite implant samples are demonstratedthat comprise 50, 60 and 70% mineral content. These samples have bothhigh mineral content and high mechanical properties.

Methods & Materials

Three types of biocomposite implants were produced: pin of outerdiameter 2 mm, pin of outer diameter 6 mm, and rectangular plates(60×27×1.5 mm). Each sample was of 7 cm length. Material composite wascomprised of PLDLA 70/30 polymer reinforced with 50% w/w, 60% w/w or 70%w/w continuous mineral fibers. Mineral fibers composition wasapproximately Na2O 14%, MgO 5.4%, CaO 9%, B2O3 2.3%, P2O5 1.5%, and SiO267.8% w/w. Testing samples were manufactured by compression molding ofmultiple layers of composite material into a tubular mold or rectangularmold. Each layer was comprised of the PLDLA polymer with embeddeduni-directionally aligned continuous fibers. Orientation of layersrelative to longitudinal axis of implant were 0° (parallel to implantlongitudinal axis), 45°, 0°, −45°, 0°, in a repetitive manner accordingto a number of layers in the implant. Each layer was approximately 0.18mm thick. Three (3) samples were produced for each group. Mechanicalproperties were tested in a three point bending test.

Results

2 mm pins Flexural E [Mpa] Strength [Mpa] Max Load [N] T0 5 days T0 5days T0 5 days 50% 11761.0055 11954.8476 273.5469 127.1556 25.664712.453 60% 17772.9284 10858.1928 339.9570 95.0317 30.5300 11.1593 70%14062.1921 9931.4495 290.5704 78.8613 30.1587 8.6517

Plates Flexural E [Mpa] Strength [Mpa] Max Load [N] T0 5 days T0 5 daysT0 5 days 50% 15362.1439 11063.2504 306.8561 127.0402 285.2700 143.500070% 23088.3630 10806.9162 358.4756 83.1500 307.5633 115.7633

6 mm pins Flexural E [Mpa] Strength [Mpa] Max Load [N] T0 5 days T0 5days T0 5 days 50% 8696.9920 6423.4802 243.6777 118.6093 549.6000267.8900 70% 14207.5159 6744.9709 224.6186 85.0544 455.0700 209.7467

Example 8—Mineral Content and Sustained Strength

In the current example, biocomposite implant samples are demonstratedthat comprise 58% and 68% mineral content. These samples have both highmineral content and high mechanical properties.

Methods & Materials

Biocomposite rectangular plate implants were produced of dimensions12.7×60×2.0 mm. Material composite was comprised of PLDLA 70/30 polymerreinforced with 58% w/w or 68% w/w mineral fibers. Mineral fiberscomposition was approximately Na₂O 14%, MgO 5.4%, CaO 9%, B₂O₃ 2.3%,P₂O₅ 1.5%, and SiO₂ 67.8% w/w. Testing samples were manufactured bycompression molding of composite material into a rectangular mold.Reinforcing mineral fibers were of a chopped nature, with fiber segmentlengths predominately in the range of 5-10 mm. Plate weight was 2.75 gon average for each plate. Ten (10) samples were produced for eachgroup. Mechanical properties were tested in a three-point bending testaccording to ASTM D790, with 5 samples from each of the 58% and 68%group being tested at time zero (t=0 days) and 5 samples from each ofthe 58% and 68% group being tested after 5 days of simulated in vitrodegradation according to modified ASTM F1635 (t=5 days at 37 deg C., 60rpm) in PBS.

Mechanical testing was performed using a 5 KN load cell and anappropriate fixture for three-point bending testing. Sample span was 40mm at the beginning of the test and cross head speed was set at 2mm/min. Dimensions and weight of the samples were recorded.

Results

2 mm 58% fiber plate from chopped raw material Average Flexural strengthAverage Maximum load [N] [MPa] T0 59.6 +/− 12.8 70.35 T5 40.9 +/− 7.7 48.28

2 mm 68% fiber plate from chopped raw material Average Flexural strengthAverage Maximum load [N] [MPa] T0 53.3 +/− 7.1 62.97 T5 30.9 +/− 4.436.49

58% mineral plates had a slightly higher Flexural strength at TO than68% plates.

After 5 days in PBS Solution under the same conditions the Flexuralstrength of the 58% plate decreased by 32% while the flexural strengthof the 68% plate decreased by 42%. Though this test was performed afteronly a few days of simulated degradation, there is a clear trend tosuggest that increasing fiber contents above 60% will reduce flexuralstrength and increase the mechanical strength loss rate over time.

It will be appreciated that various features of the invention which are,for clarity, described in the contexts of separate embodiments may alsobe provided in combination in a single embodiment. Conversely, variousfeatures of the invention which are, for brevity, described in thecontext of a single embodiment may also be provided separately or in anysuitable sub-combination. It will also be appreciated by persons skilledin the art that the present invention is not limited by what has beenparticularly shown and described hereinabove. Rather the scope of theinvention is defined only by the claims which follow.

What is claimed is:
 1. A medical implant comprising a biocomposite, saidbiocomposite comprising a polymer and a plurality of reinforcementmineral fibers, wherein a weight percentage of a mineral compositionwithin the biocomposite medical implant is in a range of 40-65%, whereinan average diameter of said fibers is in a range of 3-30 microns;wherein the reinforcing fibers are fiber segments with an average fibersegment length in the range of 0.5-20 mm; wherein a residual monomercontent in the implant following production is less than 3%; wherein themineral composition is provided by a reinforcing mineral fiber made fromthe mineral composition.
 2. The implant of claim 1, wherein said implantcomprises a silica-based mineral compound and wherein said silica-basedmineral compound has at least one oxide composition in at least one ofthe following mol. % ranges: Na₂O: 11.0-19.0 mol. % CaO: 9.0-14.0 mol. %MgO: 1.5-8.0 mol. % B₂O₃: 0.5-3.0 mol. % Al₂O₃: 0-0.8 mol. % P₂O₃:0.1-0.8 mol. % SiO₂: 67-73 mol. %.
 3. The implant of claim 2, whereinsaid silica-based mineral compound has at least one oxide composition inat least one of the following mol. % ranges: Na₂O: 11.0-19.0 mol. % CaO:9.0-14.0 mol. % MgO: 1.5-8.0 mol. % B₂O₃: 0.5-3.0 mol. % Al₂O₃: 0-0.8mol. % P₂O₃: 0.1-0.8 mol. % SiO₂: 67-73 mol. %.
 4. The implant of claim1, wherein the diameter of a majority of reinforcing fibers is in therange of 5-20 μm.
 5. The implant of claim 4, wherein the diameter is inthe range of 4-16 μm.
 6. The implant of claim 5, wherein the diameter isin the range of 9-14 μm.
 7. The implant of claim 1, wherein saidbiocomposite comprises mineral fibers are embedded in a polymer matrix;wherein said polymer comprises lactide, glycolide, caprolactone,valerolactone, carbonates, dioxanones, δ-valerolactone, 1,dioxepanones,ethylene glycol, ethylene oxide, esteramides, γ-ydroxyvalerate,β-hydroxypropionate, alpha-hydroxy acid, hydroxybuterates, poly (orthoesters), hydroxy alkanoates, tyrosine carbonates, polyimide carbonates,polyimino carbonates, poly (bisphenol A-iminocarbonate) and poly(hydroquinone-iminocarbonate), polyurethanes, polyanhydrides, polymerdrugs, sugars; starch, cellulose and cellulose derivatives,polysaccharides, collagen, chitosan, fibrin, hyaluronic acid,polypeptides, proteins, poly (amino acids), polylactides (PLA),poly-L-lactide (PLLA), poly-DL-lactide (PDLLA); polyglycolide (PGA);copolymers of glycolide, glycolide/trimethylene carbonate copolymers(PGA/TMC); other copolymers of PLA, lactide/tetramethylglycolidecopolymers, lactide/trimethylene carbonate copolymers,lactide/d-valerolactone copolymers, lactide/c-caprolactone copolymers,L-lactide/DL-lactide copolymers, glycolide/L-lactide copolymers(PGA/PLLA), polylactide-co-glycolide; terpolymers ofPLA,lactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolide/ε-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically-3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates;polyhydroxybutyrates)PHB); PHB/b-hydroxyvalerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone-poly-ε-capralactone,poly(ε-caprolactone-DL-lactide) copolymers; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinylalcohol (PVA); polypeptides; poly-b-malic acid (PMLA):poly-b-alkanbic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides); and mixtures thereof; and derivatives,copolymers and mixtures thereof.
 8. The implant of claim 7, wherein saidpolymer is selected from the group consisting of PLLA, PDLA, PGA, PLGA,PCL, PLLA-PCL and a combination thereof.
 9. The implant of claim 8,wherein said PLLA is used in said polymer matrix and said matrixcomprises at least 30%, 50% or 70% PLLA; and/or wherein said PDLA isused in said polymer matrix and said matrix comprises at least 5%, 10%or 20% PDLA.
 10. The implant of claim 9, wherein said matrix comprisesat least 20% PDLA.
 11. The implant of claim 1, wherein the implantcomprises a plurality of layers, each layer has a directional fiberorientation, and wherein said fiber orientation alternates betweenadjacent layers such that each adjacent layer is of a different angle,wherein said angle difference between layers is between 15 to 75degrees.
 12. The implant of claim 1, wherein the implant has a flexuralmodulus exceeding 12 GPa and a flexural strength exceeding 180 MPa after5 days of simulated physiological degradation.
 13. The implant of claim1, wherein said implant has a strength retention of Elastic Modulusabove 10 GPa after 8 weeks implantation and a flexural strength above150 MPa after 8 weeks implantation.
 14. The implant of claim 1, whereina moisture content of implant following production is less than 1%. 15.The implant of claim 14, wherein said moisture content is less than0.4%.
 16. The implant of claim 15, wherein said moisture content is lessthan 0.2%.
 17. The implant of claim 1, wherein said residual monomercontent is less than 2%.
 18. The implant of claim 17, wherein saidresidual monomer content is less than 1%.
 19. The implant of claim 1wherein the implant is selected from the groups including bone fixationplates, intramedullary nails, joint implants, spine implants, and otherdevices for fracture fixation, tendon reattachment, spinal fixation, andspinal cage fixation.
 20. The implant of claim 19, adapted to a threadedimplant.
 21. The implant of claim 1, wherein the average fiber segmentlength is in the range of 1-15 mm.
 22. The implant of claim 21, whereinthe length is in the range of 3-10 mm.
 23. The implant of claim 22,wherein the length is in the range of 4-8 mm.